ChemWiki - User contributions [en]

It:Anandamide

2006-12-07T13:57:01Z

Nha05:

== Introduction ==

Anandamide (which is also known as arachidonoylethanolamide) is a naturally occurring endogenous cannabinoid neurotransmitter that plays a role in pain relief, eating and sleeping patterns, depression, memory and fertility. It can be found in the organs of both humans and animals, in particular the brain. Anandamide is responsible for the narcotic effect of marijuana, which produces a natural high. It is also found in high concentrations in chocolate. Evidence suggest that periods of exercise release of cannabinoids, including anandamide, and that these chemicals contribute to 'runner's high' It is thought that Anandamide attaches to the protein receptor THC (tetrahydrocannabinol) on the membrane of cells and triggers a reaction inside the cells that makes us feel high. Anandamide is broken down fast naturally by the body but chocolate contains two substances, N-oleoylethanolamine and N-linoleoylethaolamine, which inhibit the natural breakdown of anandamide, hence preserving the natural high.

Anandamide got its name from the "''Sanskrit''" word "ananda", which means "bliss" i.e. a state of extreme happiness and amide. It was first isolated and structurally discovered in 1992, by Lumír Ondřej Hanuš and William Anthony Devane in the Laboratory of Raphael Mechoulam, at the Hebrew University.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}}| '''Anandamide'''
|-
| align="center" colspan="2" bgcolor="#ffffff" | [[Image:anandamide-struct.gif]]
|-
!{{chembox header}}| General
|-
! Systematic Chemical name
| (5Z,8Z,11Z,14Z)-N-(2-hydroxyethyl)
icosa-5,8,11,14-tetraenamide
|-
!Synonyms
| Arachidonylethanolamide(AEA)
Arachidonic acid N-(hydroxyethyl)amide
|-
!Appearance
|Light yellow oil
|-
! Chemical formula
|C<sub>22</sub>H<sub>37</sub>NO<sub>2</sub>
|-
! Molecular Weight
| 347.54
|-
! CAS number
| 94421-68-8
|-
! Smile string
|CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(NCCO)=O
|-
!{{chembox header}}| Physical Properties
|-
!Solubility
|Soluble in ethanol
|-
!Density
|0.92g/mL (at 25<sup>o</sup>C)
|-
!{{chembox header}}|Safety
|-
!Precautions
|Keep away from skin and eyes
|-
|}

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[http://c4.cabrillo.edu/features/news.html]
[[User:cn205|cn205]] 14:25, 26 October 2006 (BST)

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[[User:Smbc05|Smbc05]] 14:53, 20 October 2006 (BST)

==Structure==
Anandamide is fat-soluble due to its long hydrocarbon tail. It can pass through the hydrocarbon-rich curtain which isolates the brain from the bloodstream easily. Unlike THC, anandamide breaks down very quickly in the body; which is also the reason why anandamide does not produce an everlasting natural 'high'. [http://antoine.frostburg.edu/chem/senese/101/features/anandamide.shtml]

With the long unsaturated hydrocarbon chain, anandamide possesses a very flexible structure of 16 torsion angles allowing hundreds of conformers. However, researchs showed that the molecule lacks internal folding of the aliphatic chain and its structure is somewhere between linear and U-shaped. This may explain the function of anandamide as a ligand for cannabinoid receptors such as CB1 and CB2.
{|
|-
| align="center" colspan="2" bgcolor="#ffffff" |[[Image: Prefered_conformation_of_anandamide.jpg]] ||Summary of NMR-based structural calculation of AEA conformations in chloroform solution, 32 sets of conformational families were generated and grouped together with the cutoff energy of 36 kcal/mol, showing that AEA mainly assumes 36% of the conformers in extended pseudo helical shapes (A in a side view and a top view), 17% in the twisted “U”-shapes” (B), 17% in the “L” shapes, 6% in “Γ” shapes, and 24% in “C” shapes (E). The energy differences among these conformers are about 0.2~2.5 kcal/mol.
|-
|}

==Functions in human body==
Anandamide has certain functions in our body, and it is not as simple as producing happiness. Anandamide is synthesized in those areas in the brain that are important in memory and higher thought processes, as well as areas which control movements. Anandamide or N-arachidonoylethanolamine (AnNH) plays important roles in the nervous and immune system. Anandamide receptors were originally found due to sensitivity to Δ9-tetrahydrocannabinol (Δ9-THC), which is a component of marijuana. The chemical affects the short term memory and some human behaviour like sleeping and eating pattern and also in pain relieves. It was also found out that anadamide plays an important role in implantation of the embryo stage; hence Δ9-THC might obstruct the early stages of pregnancy.

'''Effect on Pregnancies'''

Anandamide plays an important role in implantation and development of the embryo in the human body, and it has been suggested that high levels of the chemical can contribute to problems in pregnancy such as abnormal embryonic development, problematic transportation through the oviduct, failed implantation in the uterine walls and reduced chances of survival. Heightened levels of anandamide in the body may be attributed to use of cannibis whereby THC, having a very similar structure to anandamide, can activate the Cannabinoid receptors CB1 and 2, displacing the anandamide molecule that naturally activates them.[http://www.jci.org/cgi/content/full/116/8/2087?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Herbert+Schuel&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT ]

Cannabinoid receptors sensitive to anandamide have also been found in sperm, suggesting that anandamide has a pivotal role in sperm functions during fertilisation. In fact, an extremely notable reduction of premature acrysomal reactions was observed on exposure of rats to a synthetic equivalent of the naturally occuring anandamide. The study also showed that fluctuation in anandamide levels increased or decreased the hyperactive "swimming" of sperm with low or high exposure to anandamide respectively.[http://sulcus.berkeley.edu/mcb/165_001/papers/manuscripts/_657.html]

Other than the brain, anandamide can also be found in other parts of the body, such as in the uterus. In fact, the highest concentration of anandamide found in our body is not the brain, but in the uterus just before the implantation of the embryo; and its concentration varies with the receptivity of the uterus. Anandamide acts as a chemical messenger between the embryo and uterus during the implantation of the embryo in the uterine wall, which means one of the first communications that occurs between the mother and child is carried out by anandamide. [http://antoine.frostburg.edu/chem/senese/101/features/anandamide.shtml]

'''The ligand binds to two receptors'''

Cannabinoid CB1 receptors (G-protein-coupled receptors) are found on presynaptic membranes in the brain in the nervous system. The effects are:

• Induce inhibition of forskolin-induced cAMP accumulation
• Inhibition of N-type Ca+ channels
• Activation of mitogen-activated protein kinase signal transduction pathway
• Increase in protein tyrosine phosphorylation

Cannabinoid CB2 receptors are present not in the brain in the periphery but also on cells of the immune system. The effects are:

• Inhibition of aldenylate cyclase
• Activation of the mitogen- activated proeteinkinase signaling

[[Image:Activation_of_receptor|thumb|right|200|Description of image]]

[http://www.jbc.org/cgi/reprint/273/48/32332.pdf]

==Anandamide and Chocolate==
Chocolate contains a miniscule amount of anandamide; most of which is broken down by stomach acid by the enzyme fatty acid amide hydrolase[http://www.nature.com/nature/journal/v396/n6712/full/396636a0_fs.html] upon ingestion, resulting in very little effect on the cannabinoid brain receptors. However, In 1996, Daniele Piomelli and co-workers at the Neurosciences Institute in San Diego discovered three other compounds in dark chocolate which were very similar to anandamide. Other compounds such as N-acylethanolamines were also found to block the breakdown of anandamide. Due to the inhibitation of the natural breakdown of anadamide, it may stick around in our body longer, making us feel good longer when we eat chocolate. Hence, the pleasure of chocolate is a result of the total effect of anandamide and anandamide-preserving N-acylethanolamines. [http://www.exploratorium.edu/exploring/exploring_chocolate/choc_8.html]

==Future use==
A new family of therapeutic drugs may be developed from the discovery of Anandamide. Much modern research has been directed towards producing anologues of cannabinoids that can either suppress or promote cannabinoid effects. Possible products range from neuroprotective agents to combat mental disease to pain killers to appetite suppresants and stimulants. Because it shares so many characteristics with THC, delta-9-tetrahydrocannabinol, the primary psychoactive compound in cannabis, it has been suggested as a safe alternative to this potent drug for those who need strong pain relief. In fact, anandamide could be availabel now for therapeutic uses, but the toxicology research has not been done, and the chemical cannot therefore be released onto the market as a drug. Unfortunately, the toxicology research costs millions of dollars to carry out, and no company or organisation has come forward to carry out this research. For an interview with Raphael Mechoulam Ph.D, Hebrew University of Jerusalem a leading scientist in the field of cannabinoids, see [[http://www.smart-publications.com/articles/MOM-mechoulam.php]The New Science of Cannabinoid-Based Medicine: An Interview with Dr. Raphael Mechoulam]

==Reference==

http://en.wikipedia.org/wiki/Anandamide

http://antoine.frostburg.edu/chem/senese/101/features/anandamide.shtml

http://www.exploratorium.edu/exploring/exploring_chocolate/choc_8.html

http://c4.cabrillo.edu/features/news.html

Sigma-Aldrich Online MSDS: http://www.sigmaaldrich.com/catalog/search/ProductDetail/SIGMA/A0580

C. Bonechi, A. B. V. B. M. F. A. D. C. R. (2001). Conformational analysis of <I>N</I>-arachidonylethanolamide (anandamide) using nuclear magnetic resonance and theoretical calculations. Magn. Res. Chem. 39: 432-437.

Chen, J.-Z., X.-W. Han, et al. (2005). "Preferred conformations of endogenous cannabinoid ligand anandamide." Life Sciences 76(18): 2053-2069.

[http://www.jci.org/cgi/content/full/116/8/2087?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Herbert+Schuel&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT Tuning the oviduct to the anandamide tone] Schuel, H. Journal of Clinical Investigation (2006), 116(8), 2087-2090.

[http://www.nature.com/nature/journal/v396/n6712/full/396636a0_fs.html Trick or Treat Food Cannabinoids] Nature 396, 636 (17 December 1998);

[http://sulcus.berkeley.edu/mcb/165_001/papers/manuscripts/_657.html The Positive and Negative Effects of Marijuana]

[[http://www.smart-publications.com/articles/MOM-mechoulam.php] The new science of cannabinoid based medicine]

==='''''Feel good factor in chocolates'''''===

One of the most pleasant effects of eating chocolate is the "good feeling" that many people experience after indulging. Chocolate contains more than 300 known chemicals. Scientists have been working on isolating specific chemicals and chemical combinations which may explain some of the pleasurable effects of consuming chocolate.

A neurotransmitter called anandamide, has been isolated in chocolate. Interestingly, anandamide is also produced naturally in the brain and is broken down quickly after it's produced.It was discovered that other chemicals in chocolate may inhibit the natural breakdown of anadamide. This means that natural anandamide (or introduced anandamide) may stick around longer, making us feel good longer, when we eat chocolate. However,this doesn't mean that eating chocolate will get you high, but rather that there are compounds in chocolate that may be associated with the good feeling that chocolate consumption provides.

==Synthesis of anandamide==
The main mechanism for the biosynthesis of anandamide and related amides requires as a first step the production of N-acyl-phosphatidylethanolamine, a lipid that is normally present in animal tissues at very low levels only other than during injury. Unusual transacylases reactions, rather than hydrolysis and re-synthesis via CoA esters, are involved, and the reaction is Ca2+ -dependent and energy-independent. It seems that only 1-O-acyl groups of phospholipids such as phosphatidylcholine can serve as acyl donors and that much of the acyl transfer is intramolecular, with production of a hypothetical intermediate, 2-O-acyl-sn-glycero-3-phospho-(N-acyl)-ethanolamine (or N-acyl lysoPE). The free sn-1 hydroxy group is then subjected to re-acylation, presumably by the same transacylase system. A second mechanism involves this transacylase catalysing direct transfer of the fatty acids of position 1 of phosphatidylcholine (or of other phospholipids such as cardiolipin) to N-acylate phosphatidylethanolamine. A surprising feature of this reaction is the fact that the arachidonic acid levels in position 1 of phospholipids are usually very low (typically <0.3%), other than in testis.

[[Image:Anadamide synthesis 1.gif]]

The second step in the biosynthesis of anandamide and related amides is hydrolysis of the N-acyl-phosphatidylethanolamine by a phosphodiesterase that has a similar function to phospholipase D but with different properties. In addition to anandamide, phosphatidic acid is formed, and this also has messenger functions.

[[Image: Anadamide synthesis 2.gif]]

'''A n a n d a m i d e'''

[[Image: Anandamide.jpg]]

It:Anandamide

2006-12-07T13:56:40Z

Nha05:

File:Anandamide.jpg

2006-12-07T13:56:03Z

Nha05:

It:Anandamide

2006-12-07T13:55:29Z

Nha05:

It:Anandamide

2006-12-07T13:27:31Z

Nha05:

File:Anadamide synthesis 2.gif

2006-12-07T13:26:25Z

Nha05:

It:Anandamide

2006-12-07T13:24:38Z

Nha05:

It:Anandamide

2006-12-07T13:23:21Z

Nha05:

File:Anadamide synthesis 1.gif

2006-12-07T13:16:33Z

Nha05:

It:Anandamide

2006-12-07T13:02:35Z

Nha05:

It:Roaccutane

2006-12-07T12:51:26Z

Nha05:

<jmol>
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<script>zoom 100; cpk off;frame 1; move 40 -20 20 0 0 0 0 0 3; delay 0.5;</script>
<inlineContents>roaccutane.pdb
title1
title2
ATOM 1 C1 MOL 1 14.263 13.508 0.005 1.00 0.00
ATOM 2 C2 MOL 1 15.445 12.906 0.072 1.00 0.00
ATOM 3 C3 MOL 1 12.940 12.770 -0.027 1.00 0.00
ATOM 4 C4 MOL 1 16.692 13.626 0.034 1.00 0.00
ATOM 5 C5 MOL 1 12.825 11.196 -0.135 1.00 0.00
ATOM 6 C6 MOL 1 11.833 13.525 0.052 1.00 0.00
ATOM 7 C7 MOL 1 17.817 12.921 0.063 1.00 0.00
ATOM 8 C8 MOL 1 16.708 15.125 -0.058 1.00 0.00
ATOM 9 C9 MOL 1 13.847 10.514 -1.092 1.00 0.00
ATOM 10 C10 MOL 1 13.053 10.611 1.285 1.00 0.00
ATOM 11 C11 MOL 1 11.426 10.791 -0.613 1.00 0.00
ATOM 12 C12 MOL 1 11.973 15.022 0.150 1.00 0.00
ATOM 13 C13 MOL 1 10.425 12.944 0.039 1.00 0.00
ATOM 14 C14 MOL 1 19.122 13.553 0.008 1.00 0.00
ATOM 15 C15 MOL 1 10.413 11.431 0.300 1.00 0.00
ATOM 16 C16 MOL 1 20.200 12.776 0.050 1.00 0.00
ATOM 17 C17 MOL 1 21.537 13.348 -0.007 1.00 0.00
ATOM 18 C18 MOL 1 22.581 12.508 0.048 1.00 0.00
ATOM 19 C19 MOL 1 21.682 14.844 -0.126 1.00 0.00
ATOM 20 C20 MOL 1 24.024 12.882 0.002 1.00 0.00
ATOM 21 O21 MOL 1 24.869 11.984 0.071 1.00 0.00
ATOM 22 O22 MOL 1 24.460 14.200 -0.117 1.00 0.00
TER</inlineContents>
</jmolApplet>
</jmol>

[[Image:Roaccutane.gif|thumb|right|200|Roaccutane]]

'''Roaccutane''' otherwise known as ''isoretinoin'', ''Tasmar'' or ''Teriosal''.
{| border="1"
|+
{| border="1"
! Formula !! Molecular weight !! Melting Point
|-
! C<sub>20</sub>H<sub>28</sub>O<sub>2</sub>
| 300.44 || 189-190C
|-
|}
===Interesting Fact===
'''Roaccutane''' is a form of Vitamin A prescribed by dermatologists for severe '''acne''', and it is only given to patients who have not responded to previous milder treatments. Roaccutane makes the sebaceous gland less productive, reduces the size of the sebaceous glands and the inflammation of the skin in acne.

=='''A little history of isotretinoin'''==

Oral isotretinoin was introduced in 1982 and was approved by the Food and Drug Administration (FDA)for the treatment of severe acne problems that has not responded to antibiotics.

Today, it would still be one of the most effective antiacne drug for various reasons.
Isotretinoin is a naturally occurring molecule in humans, found in every patient with acne and in women during pregnancy.

=='''How does it work?'''==

Roaccutane, also known as isotretinoin, belongs to a group of medicines known as retinoids (a derivatives vitamin A),and has IUPAC name of 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenoic acid.

Isotretinoin is an isomer of tretinoin. The only structural difference between the two molecules lies in the spatial arrangement of the atoms around one carbon-carbon double bond.

The mechanisms are not well understood, but Roaccutane was found to decrease reduce the production of the sebum by decreacing the size and activity of the sebaceous glands in the skin, thus stops the glands from becoming blocked and infected by bacteria. Isotretinoin will cause the other retinoids, arachidonic acid release from macrophages to be inhibited. This may account for the anti-inflammatory effects of retinoids.

If we follow the metabolic pathway of Vitamin A, also known as retinol,we will find that it takes part in the metabolising process of isotretinoin. Vitamin A is absorbed from the in the body and converted into retinal, which is then oxidised into retinoic acids. Isomers of retinoic acid:(retinoic acid and 1,3-cis- retinoic acid).

While isotretinoin is converted into oxo-isotretinoin, it interconverts between retionoic acid from vitamin A. These metabolites are then stored in the adipose layer of tissues.

Isotretinoion has a half life of 18.7±6.2 hours in the body.
Isotretinoin's anti-acne effects can last for months to years following a twenty week course.
Unlike antibiotic treatments, isotretinoin does not promote antibiotic-resistant bacteria.

===retinoic acid===
[[Image:Untitledretinol.gif]]

===retinal===
[[Image:Retinal.bmp]]

<jmol>
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<size>200</size>
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<script>zoom 100; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER NONAME 26-Oct-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 26-Oct-06 0 NONE 4
ATOM 1 C 0 -3.884 -1.133 -1.894 0.00 0.00 C+0
ATOM 2 C 0 -4.286 -0.952 -0.429 0.00 0.00 C+0
ATOM 3 C 0 -4.193 -2.298 0.293 0.00 0.00 C+0
ATOM 4 C 0 -3.355 0.028 0.225 0.00 0.00 C+0
ATOM 5 C 0 -2.060 -0.420 0.589 0.00 0.00 C+0
ATOM 6 C 0 -0.960 0.214 0.102 0.00 0.00 C+0
ATOM 7 C 0 0.323 -0.268 0.414 0.00 0.00 C+0
ATOM 8 C 0 0.479 -1.486 1.286 0.00 0.00 C+0
ATOM 9 C 0 1.428 0.369 -0.075 0.00 0.00 C+0
ATOM 10 C 0 2.701 -0.179 0.133 0.00 0.00 C+0
ATOM 11 C 0 3.823 0.516 -0.264 0.00 0.00 C+0
ATOM 12 C 0 5.094 -0.031 -0.056 0.00 0.00 C+0
ATOM 13 C 0 5.236 -1.379 0.602 0.00 0.00 C+0
ATOM 14 C 0 6.216 0.664 -0.453 0.00 0.00 C+0
ATOM 15 C 0 7.477 0.065 -0.367 0.00 0.00 C+0
ATOM 16 H 0 7.563 -0.970 -0.070 0.00 0.00 H+0
ATOM 17 O 0 8.475 0.709 -0.625 0.00 0.00 O+0
ATOM 18 C 0 -3.675 1.286 0.479 0.00 0.00 C+0
ATOM 19 C 0 -2.639 2.165 1.132 0.00 0.00 C+0
ATOM 20 C 0 -5.011 1.888 0.154 0.00 0.00 C+0
ATOM 21 C 0 -5.751 1.011 -0.857 0.00 0.00 C+0
ATOM 22 C 0 -5.724 -0.435 -0.357 0.00 0.00 C+0
ATOM 23 H 0 -4.556 -1.848 -2.369 0.00 0.00 H+0
ATOM 24 H 0 -3.949 -0.175 -2.410 0.00 0.00 H+0
ATOM 25 H 0 -2.861 -1.506 -1.947 0.00 0.00 H+0
ATOM 26 H 0 -3.194 -2.713 0.161 0.00 0.00 H+0
ATOM 27 H 0 -4.390 -2.154 1.355 0.00 0.00 H+0
ATOM 28 H 0 -4.930 -2.984 -0.123 0.00 0.00 H+0
ATOM 29 H 0 -1.948 -1.264 1.252 0.00 0.00 H+0
ATOM 30 H 0 -1.072 1.087 -0.523 0.00 0.00 H+0
ATOM 31 H 0 0.408 -2.384 0.672 0.00 0.00 H+0
ATOM 32 H 0 1.452 -1.459 1.778 0.00 0.00 H+0
ATOM 33 H 0 -0.308 -1.497 2.040 0.00 0.00 H+0
ATOM 34 H 0 1.321 1.294 -0.621 0.00 0.00 H+0
ATOM 35 H 0 2.803 -1.145 0.605 0.00 0.00 H+0
ATOM 36 H 0 3.721 1.482 -0.735 0.00 0.00 H+0
ATOM 37 H 0 6.292 -1.596 0.762 0.00 0.00 H+0
ATOM 38 H 0 4.716 -1.373 1.560 0.00 0.00 H+0
ATOM 39 H 0 4.802 -2.145 -0.042 0.00 0.00 H+0
ATOM 40 H 0 6.122 1.672 -0.831 0.00 0.00 H+0
ATOM 41 H 0 -2.064 2.682 0.364 0.00 0.00 H+0
ATOM 42 H 0 -3.134 2.897 1.770 0.00 0.00 H+0
ATOM 43 H 0 -1.970 1.551 1.735 0.00 0.00 H+0
ATOM 44 H 0 -5.603 1.966 1.066 0.00 0.00 H+0
ATOM 45 H 0 -4.866 2.883 -0.267 0.00 0.00 H+0
ATOM 46 H 0 -6.784 1.349 -0.948 0.00 0.00 H+0
ATOM 47 H 0 -5.256 1.073 -1.827 0.00 0.00 H+0
ATOM 48 H 0 -6.364 -1.053 -0.988 0.00 0.00 H+0
ATOM 49 H 0 -6.075 -0.473 0.674 0.00 0.00 H+0
CONECT 1 2 23 24 25 NONE 54
CONECT 2 1 22 3 4 NONE 55
CONECT 3 2 26 27 28 NONE 56
CONECT 4 2 5 18 0 NONE 57
CONECT 5 4 6 29 0 NONE 58
CONECT 6 5 7 30 0 NONE 59
CONECT 7 6 8 9 0 NONE 60
CONECT 8 7 31 32 33 NONE 61
CONECT 9 7 10 34 0 NONE 62
CONECT 10 9 11 35 0 NONE 63
CONECT 11 10 12 36 0 NONE 64
CONECT 12 11 13 14 0 NONE 65
CONECT 13 12 37 38 39 NONE 66
CONECT 14 12 15 40 0 NONE 67
CONECT 15 14 16 17 0 NONE 68
CONECT 17 15 0 0 0 NONE 69
CONECT 18 4 19 20 0 NONE 70
CONECT 19 18 41 42 43 NONE 71
CONECT 20 18 21 44 45 NONE 72
CONECT 21 20 22 46 47 NONE 73
CONECT 22 21 2 48 49 NONE 74
END</inlineContents>
</jmolApplet>
</jmol>

==='''A picture of roaccutane pill'''===
[[Image:Images.jpg]]

=='''reaction scheme'''==
[[Image:Synthesis.GIF]]

=='''Side effect and some precaution'''==
Isotretinoin causes birth defects if taken during pregnancy period.
This medicine may cause depression but rarely causes suicide attempts
Dry skin may be experienced. Dryness of the mucous membranes (lips and eyes).Disturbances in the composition of the blood may happen (increase plasma concentration).
Isotretinoin is used in combination with tetracycline-type antibiotics increases the pressure within the skull. For this reason, tetracycline antibiotics must not be taken with isotretinoin. An overdose, may cause changes in the structure of the bone. Roaccutane has a simmilar structure to vitamin A, therefore vitamin A supplements should therefore be avoided.

==References==
*[http://linkinghub.elsevier.com/retrieve/pii/S0190962298704384 ]- Journal of the American Academy of Dermatology, Volume 39, Issue 2, Pages S8-S12 U. Wiegand, R. Chou

===KIMCHI===

Roaccutane contains the active ingredient isotretinoin. This is a vitamin A derivative. Roaccutane is used to treat severe forms of acne (such as nodular orconglobate acne, or acne at risk of permanent scarring) which has not got better after other anti-acnetreatments, including oral antibiotics. Roaccutane treatment must be supervised by a dermatologist (a doctor specialised in the treatment of skin problems). Roaccutane may increase the levels of fats such as triglycerides or cholesterol in your blood. Roaccutane is teratogenic. This means that it is likely to damage an unborn baby. There is also an increased risk of miscarriage

====Properties====
Isotretinoin is a yellowish-orange crystalline powder with a melting point of about
175°C.
====Solubility====
*Water: very sparingly soluble
*Chloroform: soluble
*Methylene chloride: soluble
*Isopropanol: soluble
*Polyethylene glycol soluble
*Soy bean oil: less than 1 mg / 100 ml
Soybean oil is usually used as a suspension medium for Isotretinoin in soft gelatine capsule

[[Image: Isotretinoin.jpg]]

===''Acne drug increases cholesterol levels''===

Dermatology researches at the University of California, San Fransisco, have released the analysis of the effects caused by taking the drug isotretionin, the active ingredient in roaccutane.

The study involved 13,772 acne sufferers whose ages are between 13 and 50. They showed raised levels of triglyceride lipid esters in about 44% of the patients who used to have normal levels. 31% were reported for higher cholesterol levels. Anbormal results for liver function and cholesterol levels were also more common than expected.There was 11% increase in liver enzymes and abnormal liver tests. However, the aforementioned levels resumed to normal after discontinuing usage of the drug.

[http://www.healthynerd.com]

===''Acne drug Roaccutane linked to depression''===

Biochemist Dr Sarah Bailey looked at how healthy mice were affected by a six-week course of Roaccutane. She found that when given levels of Roaccutane equivalent to those used to treat teenagers, the creatures developed symptoms of depression, stress or despair.

It is not yet clear how the drug, which belongs to a family of compounds called retinoids, causes depression. It is thought it may lower levels of serotonin, a brain chemical known to boost people's mood. Alternatively, Roaccutane may reduce the formation of new brain cells - something some experts believe may cause depression.

Dr Bailey looked at how adolescent mice - picked because they were in a similar stage of development to teenage children - reacted to regular doses of Roaccutane. The mice took part in two experiments. In the first, they were placed in a tank of water that was slightly too deep for them. Usually, mice try to escape, either by swimming or trying to climb out of the tank. But, these mice spent more time than expected completely still.

A second experiment, in which the creatures had to try to right themselves after being placed upside down, confirmed they had lost their will to fight.

[http://www.injurywatch.co.uk/news-and-groups/news/medical-health]

===Adverse effects===
Most adverse effects resemble vitamin A toxicity. Adverse drug reactions associated with isotretinoin therapy include:[1]

*Common: mild acne flare, dryness of skin, lips and mucous membranes, cheilitis, itch, skin fragility, skin peeling, rash, flushing, photosensitivity, nose bleeds, dry eyes, eye irritation, conjunctivitis, reduced tolerance to contact lenses, hyperlipidaemia, raised liver enzymes, headaches, hair thinning, myalgia and/or arthralgia.
*Infrequent: severe acne flare, raised blood glucose level, increased erythrocyte sedimentation rate, fatigue and/or mood changes.
*Rare: impaired night vision, cataracts, optic neuritis, menstrual disturbances, inflammatory bowel disease, pancreatitis, hepatitis, corneal opacities, papilloedema, idiopathic intracranial hypertension, skeletal hyperostosis and extraosseous calcification.
The following adverse effects have been reported to persist, even after discontinuing therapy: alopecia (hair loss), arthralgias, decreased night vision, degenerative disc disease, keloids, bone disease, depression (in some cases). High dosages of isotretinoin have been reported to cause rosacea.

It:Roaccutane

2006-12-07T12:43:34Z

Nha05:

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<script>zoom 100; cpk off;frame 1; move 40 -20 20 0 0 0 0 0 3; delay 0.5;</script>
<inlineContents>roaccutane.pdb
title1
title2
ATOM 1 C1 MOL 1 14.263 13.508 0.005 1.00 0.00
ATOM 2 C2 MOL 1 15.445 12.906 0.072 1.00 0.00
ATOM 3 C3 MOL 1 12.940 12.770 -0.027 1.00 0.00
ATOM 4 C4 MOL 1 16.692 13.626 0.034 1.00 0.00
ATOM 5 C5 MOL 1 12.825 11.196 -0.135 1.00 0.00
ATOM 6 C6 MOL 1 11.833 13.525 0.052 1.00 0.00
ATOM 7 C7 MOL 1 17.817 12.921 0.063 1.00 0.00
ATOM 8 C8 MOL 1 16.708 15.125 -0.058 1.00 0.00
ATOM 9 C9 MOL 1 13.847 10.514 -1.092 1.00 0.00
ATOM 10 C10 MOL 1 13.053 10.611 1.285 1.00 0.00
ATOM 11 C11 MOL 1 11.426 10.791 -0.613 1.00 0.00
ATOM 12 C12 MOL 1 11.973 15.022 0.150 1.00 0.00
ATOM 13 C13 MOL 1 10.425 12.944 0.039 1.00 0.00
ATOM 14 C14 MOL 1 19.122 13.553 0.008 1.00 0.00
ATOM 15 C15 MOL 1 10.413 11.431 0.300 1.00 0.00
ATOM 16 C16 MOL 1 20.200 12.776 0.050 1.00 0.00
ATOM 17 C17 MOL 1 21.537 13.348 -0.007 1.00 0.00
ATOM 18 C18 MOL 1 22.581 12.508 0.048 1.00 0.00
ATOM 19 C19 MOL 1 21.682 14.844 -0.126 1.00 0.00
ATOM 20 C20 MOL 1 24.024 12.882 0.002 1.00 0.00
ATOM 21 O21 MOL 1 24.869 11.984 0.071 1.00 0.00
ATOM 22 O22 MOL 1 24.460 14.200 -0.117 1.00 0.00
TER</inlineContents>
</jmolApplet>
</jmol>

[[Image:Roaccutane.gif|thumb|right|200|Roaccutane]]

'''Roaccutane''' otherwise known as ''isoretinoin'', ''Tasmar'' or ''Teriosal''.
{| border="1"
|+
{| border="1"
! Formula !! Molecular weight !! Melting Point
|-
! C<sub>20</sub>H<sub>28</sub>O<sub>2</sub>
| 300.44 || 189-190C
|-
|}
===Interesting Fact===
'''Roaccutane''' is a form of Vitamin A prescribed by dermatologists for severe '''acne''', and it is only given to patients who have not responded to previous milder treatments. Roaccutane makes the sebaceous gland less productive, reduces the size of the sebaceous glands and the inflammation of the skin in acne.

=='''A little history of isotretinoin'''==

Oral isotretinoin was introduced in 1982 and was approved by the Food and Drug Administration (FDA)for the treatment of severe acne problems that has not responded to antibiotics.

Today, it would still be one of the most effective antiacne drug for various reasons.
Isotretinoin is a naturally occurring molecule in humans, found in every patient with acne and in women during pregnancy.

=='''How does it work?'''==

Roaccutane, also known as isotretinoin, belongs to a group of medicines known as retinoids (a derivatives vitamin A),and has IUPAC name of 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenoic acid.

Isotretinoin is an isomer of tretinoin. The only structural difference between the two molecules lies in the spatial arrangement of the atoms around one carbon-carbon double bond.

The mechanisms are not well understood, but Roaccutane was found to decrease reduce the production of the sebum by decreacing the size and activity of the sebaceous glands in the skin, thus stops the glands from becoming blocked and infected by bacteria. Isotretinoin will cause the other retinoids, arachidonic acid release from macrophages to be inhibited. This may account for the anti-inflammatory effects of retinoids.

If we follow the metabolic pathway of Vitamin A, also known as retinol,we will find that it takes part in the metabolising process of isotretinoin. Vitamin A is absorbed from the in the body and converted into retinal, which is then oxidised into retinoic acids. Isomers of retinoic acid:(retinoic acid and 1,3-cis- retinoic acid).

While isotretinoin is converted into oxo-isotretinoin, it interconverts between retionoic acid from vitamin A. These metabolites are then stored in the adipose layer of tissues.

Isotretinoion has a half life of 18.7±6.2 hours in the body.
Isotretinoin's anti-acne effects can last for months to years following a twenty week course.
Unlike antibiotic treatments, isotretinoin does not promote antibiotic-resistant bacteria.

===retinoic acid===
[[Image:Untitledretinol.gif]]

===retinal===
[[Image:Retinal.bmp]]

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 100; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER NONAME 26-Oct-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 26-Oct-06 0 NONE 4
ATOM 1 C 0 -3.884 -1.133 -1.894 0.00 0.00 C+0
ATOM 2 C 0 -4.286 -0.952 -0.429 0.00 0.00 C+0
ATOM 3 C 0 -4.193 -2.298 0.293 0.00 0.00 C+0
ATOM 4 C 0 -3.355 0.028 0.225 0.00 0.00 C+0
ATOM 5 C 0 -2.060 -0.420 0.589 0.00 0.00 C+0
ATOM 6 C 0 -0.960 0.214 0.102 0.00 0.00 C+0
ATOM 7 C 0 0.323 -0.268 0.414 0.00 0.00 C+0
ATOM 8 C 0 0.479 -1.486 1.286 0.00 0.00 C+0
ATOM 9 C 0 1.428 0.369 -0.075 0.00 0.00 C+0
ATOM 10 C 0 2.701 -0.179 0.133 0.00 0.00 C+0
ATOM 11 C 0 3.823 0.516 -0.264 0.00 0.00 C+0
ATOM 12 C 0 5.094 -0.031 -0.056 0.00 0.00 C+0
ATOM 13 C 0 5.236 -1.379 0.602 0.00 0.00 C+0
ATOM 14 C 0 6.216 0.664 -0.453 0.00 0.00 C+0
ATOM 15 C 0 7.477 0.065 -0.367 0.00 0.00 C+0
ATOM 16 H 0 7.563 -0.970 -0.070 0.00 0.00 H+0
ATOM 17 O 0 8.475 0.709 -0.625 0.00 0.00 O+0
ATOM 18 C 0 -3.675 1.286 0.479 0.00 0.00 C+0
ATOM 19 C 0 -2.639 2.165 1.132 0.00 0.00 C+0
ATOM 20 C 0 -5.011 1.888 0.154 0.00 0.00 C+0
ATOM 21 C 0 -5.751 1.011 -0.857 0.00 0.00 C+0
ATOM 22 C 0 -5.724 -0.435 -0.357 0.00 0.00 C+0
ATOM 23 H 0 -4.556 -1.848 -2.369 0.00 0.00 H+0
ATOM 24 H 0 -3.949 -0.175 -2.410 0.00 0.00 H+0
ATOM 25 H 0 -2.861 -1.506 -1.947 0.00 0.00 H+0
ATOM 26 H 0 -3.194 -2.713 0.161 0.00 0.00 H+0
ATOM 27 H 0 -4.390 -2.154 1.355 0.00 0.00 H+0
ATOM 28 H 0 -4.930 -2.984 -0.123 0.00 0.00 H+0
ATOM 29 H 0 -1.948 -1.264 1.252 0.00 0.00 H+0
ATOM 30 H 0 -1.072 1.087 -0.523 0.00 0.00 H+0
ATOM 31 H 0 0.408 -2.384 0.672 0.00 0.00 H+0
ATOM 32 H 0 1.452 -1.459 1.778 0.00 0.00 H+0
ATOM 33 H 0 -0.308 -1.497 2.040 0.00 0.00 H+0
ATOM 34 H 0 1.321 1.294 -0.621 0.00 0.00 H+0
ATOM 35 H 0 2.803 -1.145 0.605 0.00 0.00 H+0
ATOM 36 H 0 3.721 1.482 -0.735 0.00 0.00 H+0
ATOM 37 H 0 6.292 -1.596 0.762 0.00 0.00 H+0
ATOM 38 H 0 4.716 -1.373 1.560 0.00 0.00 H+0
ATOM 39 H 0 4.802 -2.145 -0.042 0.00 0.00 H+0
ATOM 40 H 0 6.122 1.672 -0.831 0.00 0.00 H+0
ATOM 41 H 0 -2.064 2.682 0.364 0.00 0.00 H+0
ATOM 42 H 0 -3.134 2.897 1.770 0.00 0.00 H+0
ATOM 43 H 0 -1.970 1.551 1.735 0.00 0.00 H+0
ATOM 44 H 0 -5.603 1.966 1.066 0.00 0.00 H+0
ATOM 45 H 0 -4.866 2.883 -0.267 0.00 0.00 H+0
ATOM 46 H 0 -6.784 1.349 -0.948 0.00 0.00 H+0
ATOM 47 H 0 -5.256 1.073 -1.827 0.00 0.00 H+0
ATOM 48 H 0 -6.364 -1.053 -0.988 0.00 0.00 H+0
ATOM 49 H 0 -6.075 -0.473 0.674 0.00 0.00 H+0
CONECT 1 2 23 24 25 NONE 54
CONECT 2 1 22 3 4 NONE 55
CONECT 3 2 26 27 28 NONE 56
CONECT 4 2 5 18 0 NONE 57
CONECT 5 4 6 29 0 NONE 58
CONECT 6 5 7 30 0 NONE 59
CONECT 7 6 8 9 0 NONE 60
CONECT 8 7 31 32 33 NONE 61
CONECT 9 7 10 34 0 NONE 62
CONECT 10 9 11 35 0 NONE 63
CONECT 11 10 12 36 0 NONE 64
CONECT 12 11 13 14 0 NONE 65
CONECT 13 12 37 38 39 NONE 66
CONECT 14 12 15 40 0 NONE 67
CONECT 15 14 16 17 0 NONE 68
CONECT 17 15 0 0 0 NONE 69
CONECT 18 4 19 20 0 NONE 70
CONECT 19 18 41 42 43 NONE 71
CONECT 20 18 21 44 45 NONE 72
CONECT 21 20 22 46 47 NONE 73
CONECT 22 21 2 48 49 NONE 74
END</inlineContents>
</jmolApplet>
</jmol>

==='''A picture of roaccutane pill'''===
[[Image:Images.jpg]]

=='''reaction scheme'''==
[[Image:Synthesis.GIF]]

=='''Side effect and some precaution'''==
Isotretinoin causes birth defects if taken during pregnancy period.
This medicine may cause depression but rarely causes suicide attempts
Dry skin may be experienced. Dryness of the mucous membranes (lips and eyes).Disturbances in the composition of the blood may happen (increase plasma concentration).
Isotretinoin is used in combination with tetracycline-type antibiotics increases the pressure within the skull. For this reason, tetracycline antibiotics must not be taken with isotretinoin. An overdose, may cause changes in the structure of the bone. Roaccutane has a simmilar structure to vitamin A, therefore vitamin A supplements should therefore be avoided.

==References==
*[http://linkinghub.elsevier.com/retrieve/pii/S0190962298704384 ]- Journal of the American Academy of Dermatology, Volume 39, Issue 2, Pages S8-S12 U. Wiegand, R. Chou

===KIMCHI===

Roaccutane contains the active ingredient isotretinoin. This is a vitamin A derivative. Roaccutane is used to treat severe forms of acne (such as nodular orconglobate acne, or acne at risk of permanent scarring) which has not got better after other anti-acnetreatments, including oral antibiotics. Roaccutane treatment must be supervised by a dermatologist (a doctor specialised in the treatment of skin problems). Roaccutane may increase the levels of fats such as triglycerides or cholesterol in your blood. Roaccutane is teratogenic. This means that it is likely to damage an unborn baby. There is also an increased risk of miscarriage

====Properties====
Isotretinoin is a yellowish-orange crystalline powder with a melting point of about
175°C.
====Solubility====
*Water: very sparingly soluble
*Chloroform: soluble
*Methylene chloride: soluble
*Isopropanol: soluble
*Polyethylene glycol soluble
*Soy bean oil: less than 1 mg / 100 ml
Soybean oil is usually used as a suspension medium for Isotretinoin in soft gelatine capsule

[[Image: Isotretinoin.jpg]]

===''Acne drug increases cholesterol levels''===

Dermatology researches at the University of California, San Fransisco, have released the analysis of the effects caused by taking the drug isotretionin, the active ingredient in roaccutane.

The study involved 13,772 acne sufferers whose ages are between 13 and 50. They showed raised levels of triglyceride lipid esters in about 44% of the patients who used to have normal levels. 31% were reported for higher cholesterol levels. Anbormal results for liver function and cholesterol levels were also more common than expected.There was 11% increase in liver enzymes and abnormal liver tests. However, the aforementioned levels resumed to normal after discontinuing usage of the drug.

===''Acne drug Roaccutane linked to depression''===

Biochemist Dr Sarah Bailey looked at how healthy mice were affected by a six-week course of Roaccutane. She found that when given levels of Roaccutane equivalent to those used to treat teenagers, the creatures developed symptoms of depression, stress or despair.

It is not yet clear how the drug, which belongs to a family of compounds called retinoids, causes depression. It is thought it may lower levels of serotonin, a brain chemical known to boost people's mood. Alternatively, Roaccutane may reduce the formation of new brain cells - something some experts believe may cause depression.

Dr Bailey looked at how adolescent mice - picked because they were in a similar stage of development to teenage children - reacted to regular doses of Roaccutane. The mice took part in two experiments. In the first, they were placed in a tank of water that was slightly too deep for them. Usually, mice try to escape, either by swimming or trying to climb out of the tank. But, these mice spent more time than expected completely still.

A second experiment, in which the creatures had to try to right themselves after being placed upside down, confirmed they had lost their will to fight.

[http://www.injurywatch.co.uk/news-and-groups/news/medical-health]

It:Roaccutane

2006-12-07T12:25:52Z

Nha05:

It:Roaccutane

2006-12-07T12:24:37Z

Nha05:

<jmol>
<jmolApplet>
<size>300</size>
<color>black</color>
<script>zoom 100; cpk off;frame 1; move 40 -20 20 0 0 0 0 0 3; delay 0.5;</script>
<inlineContents>roaccutane.pdb
title1
title2
ATOM 1 C1 MOL 1 14.263 13.508 0.005 1.00 0.00
ATOM 2 C2 MOL 1 15.445 12.906 0.072 1.00 0.00
ATOM 3 C3 MOL 1 12.940 12.770 -0.027 1.00 0.00
ATOM 4 C4 MOL 1 16.692 13.626 0.034 1.00 0.00
ATOM 5 C5 MOL 1 12.825 11.196 -0.135 1.00 0.00
ATOM 6 C6 MOL 1 11.833 13.525 0.052 1.00 0.00
ATOM 7 C7 MOL 1 17.817 12.921 0.063 1.00 0.00
ATOM 8 C8 MOL 1 16.708 15.125 -0.058 1.00 0.00
ATOM 9 C9 MOL 1 13.847 10.514 -1.092 1.00 0.00
ATOM 10 C10 MOL 1 13.053 10.611 1.285 1.00 0.00
ATOM 11 C11 MOL 1 11.426 10.791 -0.613 1.00 0.00
ATOM 12 C12 MOL 1 11.973 15.022 0.150 1.00 0.00
ATOM 13 C13 MOL 1 10.425 12.944 0.039 1.00 0.00
ATOM 14 C14 MOL 1 19.122 13.553 0.008 1.00 0.00
ATOM 15 C15 MOL 1 10.413 11.431 0.300 1.00 0.00
ATOM 16 C16 MOL 1 20.200 12.776 0.050 1.00 0.00
ATOM 17 C17 MOL 1 21.537 13.348 -0.007 1.00 0.00
ATOM 18 C18 MOL 1 22.581 12.508 0.048 1.00 0.00
ATOM 19 C19 MOL 1 21.682 14.844 -0.126 1.00 0.00
ATOM 20 C20 MOL 1 24.024 12.882 0.002 1.00 0.00
ATOM 21 O21 MOL 1 24.869 11.984 0.071 1.00 0.00
ATOM 22 O22 MOL 1 24.460 14.200 -0.117 1.00 0.00
TER</inlineContents>
</jmolApplet>
</jmol>

[[Image:Roaccutane.gif|thumb|right|200|Roaccutane]]

'''Roaccutane''' otherwise known as ''isoretinoin'', ''Tasmar'' or ''Teriosal''.
{| border="1"
|+
{| border="1"
! Formula !! Molecular weight !! Melting Point
|-
! C<sub>20</sub>H<sub>28</sub>O<sub>2</sub>
| 300.44 || 189-190C
|-
|}
===Interesting Fact===
'''Roaccutane''' is a form of Vitamin A prescribed by dermatologists for severe '''acne''', and it is only given to patients who have not responded to previous milder treatments. Roaccutane makes the sebaceous gland less productive, reduces the size of the sebaceous glands and the inflammation of the skin in acne.

=='''A little history of isotretinoin'''==

Oral isotretinoin was introduced in 1982 and was approved by the Food and Drug Administration (FDA)for the treatment of severe acne problems that has not responded to antibiotics.

Today, it would still be one of the most effective antiacne drug for various reasons.
Isotretinoin is a naturally occurring molecule in humans, found in every patient with acne and in women during pregnancy.

=='''How does it work?'''==

Roaccutane, also known as isotretinoin, belongs to a group of medicines known as retinoids (a derivatives vitamin A),and has IUPAC name of 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenoic acid.

Isotretinoin is an isomer of tretinoin. The only structural difference between the two molecules lies in the spatial arrangement of the atoms around one carbon-carbon double bond.

The mechanisms are not well understood, but Roaccutane was found to decrease reduce the production of the sebum by decreacing the size and activity of the sebaceous glands in the skin, thus stops the glands from becoming blocked and infected by bacteria. Isotretinoin will cause the other retinoids, arachidonic acid release from macrophages to be inhibited. This may account for the anti-inflammatory effects of retinoids.

If we follow the metabolic pathway of Vitamin A, also known as retinol,we will find that it takes part in the metabolising process of isotretinoin. Vitamin A is absorbed from the in the body and converted into retinal, which is then oxidised into retinoic acids. Isomers of retinoic acid:(retinoic acid and 1,3-cis- retinoic acid).

While isotretinoin is converted into oxo-isotretinoin, it interconverts between retionoic acid from vitamin A. These metabolites are then stored in the adipose layer of tissues.

Isotretinoion has a half life of 18.7±6.2 hours in the body.
Isotretinoin's anti-acne effects can last for months to years following a twenty week course.
Unlike antibiotic treatments, isotretinoin does not promote antibiotic-resistant bacteria.

===retinoic acid===
[[Image:Untitledretinol.gif]]

===retinal===
[[Image:Retinal.bmp]]

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 100; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER NONAME 26-Oct-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 26-Oct-06 0 NONE 4
ATOM 1 C 0 -3.884 -1.133 -1.894 0.00 0.00 C+0
ATOM 2 C 0 -4.286 -0.952 -0.429 0.00 0.00 C+0
ATOM 3 C 0 -4.193 -2.298 0.293 0.00 0.00 C+0
ATOM 4 C 0 -3.355 0.028 0.225 0.00 0.00 C+0
ATOM 5 C 0 -2.060 -0.420 0.589 0.00 0.00 C+0
ATOM 6 C 0 -0.960 0.214 0.102 0.00 0.00 C+0
ATOM 7 C 0 0.323 -0.268 0.414 0.00 0.00 C+0
ATOM 8 C 0 0.479 -1.486 1.286 0.00 0.00 C+0
ATOM 9 C 0 1.428 0.369 -0.075 0.00 0.00 C+0
ATOM 10 C 0 2.701 -0.179 0.133 0.00 0.00 C+0
ATOM 11 C 0 3.823 0.516 -0.264 0.00 0.00 C+0
ATOM 12 C 0 5.094 -0.031 -0.056 0.00 0.00 C+0
ATOM 13 C 0 5.236 -1.379 0.602 0.00 0.00 C+0
ATOM 14 C 0 6.216 0.664 -0.453 0.00 0.00 C+0
ATOM 15 C 0 7.477 0.065 -0.367 0.00 0.00 C+0
ATOM 16 H 0 7.563 -0.970 -0.070 0.00 0.00 H+0
ATOM 17 O 0 8.475 0.709 -0.625 0.00 0.00 O+0
ATOM 18 C 0 -3.675 1.286 0.479 0.00 0.00 C+0
ATOM 19 C 0 -2.639 2.165 1.132 0.00 0.00 C+0
ATOM 20 C 0 -5.011 1.888 0.154 0.00 0.00 C+0
ATOM 21 C 0 -5.751 1.011 -0.857 0.00 0.00 C+0
ATOM 22 C 0 -5.724 -0.435 -0.357 0.00 0.00 C+0
ATOM 23 H 0 -4.556 -1.848 -2.369 0.00 0.00 H+0
ATOM 24 H 0 -3.949 -0.175 -2.410 0.00 0.00 H+0
ATOM 25 H 0 -2.861 -1.506 -1.947 0.00 0.00 H+0
ATOM 26 H 0 -3.194 -2.713 0.161 0.00 0.00 H+0
ATOM 27 H 0 -4.390 -2.154 1.355 0.00 0.00 H+0
ATOM 28 H 0 -4.930 -2.984 -0.123 0.00 0.00 H+0
ATOM 29 H 0 -1.948 -1.264 1.252 0.00 0.00 H+0
ATOM 30 H 0 -1.072 1.087 -0.523 0.00 0.00 H+0
ATOM 31 H 0 0.408 -2.384 0.672 0.00 0.00 H+0
ATOM 32 H 0 1.452 -1.459 1.778 0.00 0.00 H+0
ATOM 33 H 0 -0.308 -1.497 2.040 0.00 0.00 H+0
ATOM 34 H 0 1.321 1.294 -0.621 0.00 0.00 H+0
ATOM 35 H 0 2.803 -1.145 0.605 0.00 0.00 H+0
ATOM 36 H 0 3.721 1.482 -0.735 0.00 0.00 H+0
ATOM 37 H 0 6.292 -1.596 0.762 0.00 0.00 H+0
ATOM 38 H 0 4.716 -1.373 1.560 0.00 0.00 H+0
ATOM 39 H 0 4.802 -2.145 -0.042 0.00 0.00 H+0
ATOM 40 H 0 6.122 1.672 -0.831 0.00 0.00 H+0
ATOM 41 H 0 -2.064 2.682 0.364 0.00 0.00 H+0
ATOM 42 H 0 -3.134 2.897 1.770 0.00 0.00 H+0
ATOM 43 H 0 -1.970 1.551 1.735 0.00 0.00 H+0
ATOM 44 H 0 -5.603 1.966 1.066 0.00 0.00 H+0
ATOM 45 H 0 -4.866 2.883 -0.267 0.00 0.00 H+0
ATOM 46 H 0 -6.784 1.349 -0.948 0.00 0.00 H+0
ATOM 47 H 0 -5.256 1.073 -1.827 0.00 0.00 H+0
ATOM 48 H 0 -6.364 -1.053 -0.988 0.00 0.00 H+0
ATOM 49 H 0 -6.075 -0.473 0.674 0.00 0.00 H+0
CONECT 1 2 23 24 25 NONE 54
CONECT 2 1 22 3 4 NONE 55
CONECT 3 2 26 27 28 NONE 56
CONECT 4 2 5 18 0 NONE 57
CONECT 5 4 6 29 0 NONE 58
CONECT 6 5 7 30 0 NONE 59
CONECT 7 6 8 9 0 NONE 60
CONECT 8 7 31 32 33 NONE 61
CONECT 9 7 10 34 0 NONE 62
CONECT 10 9 11 35 0 NONE 63
CONECT 11 10 12 36 0 NONE 64
CONECT 12 11 13 14 0 NONE 65
CONECT 13 12 37 38 39 NONE 66
CONECT 14 12 15 40 0 NONE 67
CONECT 15 14 16 17 0 NONE 68
CONECT 17 15 0 0 0 NONE 69
CONECT 18 4 19 20 0 NONE 70
CONECT 19 18 41 42 43 NONE 71
CONECT 20 18 21 44 45 NONE 72
CONECT 21 20 22 46 47 NONE 73
CONECT 22 21 2 48 49 NONE 74
END</inlineContents>
</jmolApplet>
</jmol>

==='''A picture of roaccutane pill'''===
[[Image:Images.jpg]]

=='''reaction scheme'''==
[[Image:Synthesis.GIF]]

=='''Side effect and some precaution'''==
Isotretinoin causes birth defects if taken during pregnancy period.
This medicine may cause depression but rarely causes suicide attempts
Dry skin may be experienced. Dryness of the mucous membranes (lips and eyes).Disturbances in the composition of the blood may happen (increase plasma concentration).
Isotretinoin is used in combination with tetracycline-type antibiotics increases the pressure within the skull. For this reason, tetracycline antibiotics must not be taken with isotretinoin. An overdose, may cause changes in the structure of the bone. Roaccutane has a simmilar structure to vitamin A, therefore vitamin A supplements should therefore be avoided.

==References==
*[http://linkinghub.elsevier.com/retrieve/pii/S0190962298704384 ]- Journal of the American Academy of Dermatology, Volume 39, Issue 2, Pages S8-S12 U. Wiegand, R. Chou

===KIMCHI===

Roaccutane contains the active ingredient isotretinoin. This is a vitamin A derivative. Roaccutane is used to treat severe forms of acne (such as nodular orconglobate acne, or acne at risk of permanent scarring) which has not got better after other anti-acnetreatments, including oral antibiotics. Roaccutane treatment must be supervised by a dermatologist (a doctor specialised in the treatment of skin problems). Roaccutane may increase the levels of fats such as triglycerides or cholesterol in your blood. Roaccutane is teratogenic. This means that it is likely to damage an unborn baby. There is also an increased risk of miscarriage

===Physical and chemical properties===
Isotretinoin is a yellowish-orange crystalline powder with a melting point of about
175°C.
=====Solubility=====
*Water: very sparingly soluble
*Chloroform: soluble
*Methylene chloride: soluble
*Isopropanol: soluble
*Polyethylene glycol soluble
*Soy bean oil: less than 1 mg / 100 ml
Soybean oil is usually used as a suspension medium for Isotretinoin in soft gelatine capsule

[[Image: Isotretinoin.jpg]]

===''Acne drug increases cholesterol levels''===

Dermatology researches at the University of California, San Fransisco, have released the analysis of the effects caused by taking the drug isotretionin, the active ingredient in roaccutane.

The study involved 13,772 acne sufferers whose ages are between 13 and 50. They showed raised levels of triglyceride lipid esters in about 44% of the patients who used to have normal levels. 31% were reported for higher cholesterol levels. Anbormal results for liver function and cholesterol levels were also more common than expected.There was 11% increase in liver enzymes and abnormal liver tests. However, the aforementioned levels resumed to normal after discontinuing usage of the drug.

It:Roaccutane

2006-12-07T12:23:01Z

Nha05:

<jmol>
<jmolApplet>
<size>300</size>
<color>black</color>
<script>zoom 100; cpk off;frame 1; move 40 -20 20 0 0 0 0 0 3; delay 0.5;</script>
<inlineContents>roaccutane.pdb
title1
title2
ATOM 1 C1 MOL 1 14.263 13.508 0.005 1.00 0.00
ATOM 2 C2 MOL 1 15.445 12.906 0.072 1.00 0.00
ATOM 3 C3 MOL 1 12.940 12.770 -0.027 1.00 0.00
ATOM 4 C4 MOL 1 16.692 13.626 0.034 1.00 0.00
ATOM 5 C5 MOL 1 12.825 11.196 -0.135 1.00 0.00
ATOM 6 C6 MOL 1 11.833 13.525 0.052 1.00 0.00
ATOM 7 C7 MOL 1 17.817 12.921 0.063 1.00 0.00
ATOM 8 C8 MOL 1 16.708 15.125 -0.058 1.00 0.00
ATOM 9 C9 MOL 1 13.847 10.514 -1.092 1.00 0.00
ATOM 10 C10 MOL 1 13.053 10.611 1.285 1.00 0.00
ATOM 11 C11 MOL 1 11.426 10.791 -0.613 1.00 0.00
ATOM 12 C12 MOL 1 11.973 15.022 0.150 1.00 0.00
ATOM 13 C13 MOL 1 10.425 12.944 0.039 1.00 0.00
ATOM 14 C14 MOL 1 19.122 13.553 0.008 1.00 0.00
ATOM 15 C15 MOL 1 10.413 11.431 0.300 1.00 0.00
ATOM 16 C16 MOL 1 20.200 12.776 0.050 1.00 0.00
ATOM 17 C17 MOL 1 21.537 13.348 -0.007 1.00 0.00
ATOM 18 C18 MOL 1 22.581 12.508 0.048 1.00 0.00
ATOM 19 C19 MOL 1 21.682 14.844 -0.126 1.00 0.00
ATOM 20 C20 MOL 1 24.024 12.882 0.002 1.00 0.00
ATOM 21 O21 MOL 1 24.869 11.984 0.071 1.00 0.00
ATOM 22 O22 MOL 1 24.460 14.200 -0.117 1.00 0.00
TER</inlineContents>
</jmolApplet>
</jmol>

[[Image:Roaccutane.gif|thumb|right|200|Roaccutane]]

'''Roaccutane''' otherwise known as ''isoretinoin'', ''Tasmar'' or ''Teriosal''.
{| border="1"
|+
{| border="1"
! Formula !! Molecular weight !! Melting Point
|-
! C<sub>20</sub>H<sub>28</sub>O<sub>2</sub>
| 300.44 || 189-190C
|-
|}
===Interesting Fact===
'''Roaccutane''' is a form of Vitamin A prescribed by dermatologists for severe '''acne''', and it is only given to patients who have not responded to previous milder treatments. Roaccutane makes the sebaceous gland less productive, reduces the size of the sebaceous glands and the inflammation of the skin in acne.

=='''A little history of isotretinoin'''==

Oral isotretinoin was introduced in 1982 and was approved by the Food and Drug Administration (FDA)for the treatment of severe acne problems that has not responded to antibiotics.

Today, it would still be one of the most effective antiacne drug for various reasons.
Isotretinoin is a naturally occurring molecule in humans, found in every patient with acne and in women during pregnancy.

=='''How does it work?'''==

Roaccutane, also known as isotretinoin, belongs to a group of medicines known as retinoids (a derivatives vitamin A),and has IUPAC name of 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenoic acid.

Isotretinoin is an isomer of tretinoin. The only structural difference between the two molecules lies in the spatial arrangement of the atoms around one carbon-carbon double bond.

The mechanisms are not well understood, but Roaccutane was found to decrease reduce the production of the sebum by decreacing the size and activity of the sebaceous glands in the skin, thus stops the glands from becoming blocked and infected by bacteria. Isotretinoin will cause the other retinoids, arachidonic acid release from macrophages to be inhibited. This may account for the anti-inflammatory effects of retinoids.

If we follow the metabolic pathway of Vitamin A, also known as retinol,we will find that it takes part in the metabolising process of isotretinoin. Vitamin A is absorbed from the in the body and converted into retinal, which is then oxidised into retinoic acids. Isomers of retinoic acid:(retinoic acid and 1,3-cis- retinoic acid).

While isotretinoin is converted into oxo-isotretinoin, it interconverts between retionoic acid from vitamin A. These metabolites are then stored in the adipose layer of tissues.

Isotretinoion has a half life of 18.7±6.2 hours in the body.
Isotretinoin's anti-acne effects can last for months to years following a twenty week course.
Unlike antibiotic treatments, isotretinoin does not promote antibiotic-resistant bacteria.

===retinoic acid===
[[Image:Untitledretinol.gif]]

===retinal===
[[Image:Retinal.bmp]]

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 100; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER NONAME 26-Oct-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 26-Oct-06 0 NONE 4
ATOM 1 C 0 -3.884 -1.133 -1.894 0.00 0.00 C+0
ATOM 2 C 0 -4.286 -0.952 -0.429 0.00 0.00 C+0
ATOM 3 C 0 -4.193 -2.298 0.293 0.00 0.00 C+0
ATOM 4 C 0 -3.355 0.028 0.225 0.00 0.00 C+0
ATOM 5 C 0 -2.060 -0.420 0.589 0.00 0.00 C+0
ATOM 6 C 0 -0.960 0.214 0.102 0.00 0.00 C+0
ATOM 7 C 0 0.323 -0.268 0.414 0.00 0.00 C+0
ATOM 8 C 0 0.479 -1.486 1.286 0.00 0.00 C+0
ATOM 9 C 0 1.428 0.369 -0.075 0.00 0.00 C+0
ATOM 10 C 0 2.701 -0.179 0.133 0.00 0.00 C+0
ATOM 11 C 0 3.823 0.516 -0.264 0.00 0.00 C+0
ATOM 12 C 0 5.094 -0.031 -0.056 0.00 0.00 C+0
ATOM 13 C 0 5.236 -1.379 0.602 0.00 0.00 C+0
ATOM 14 C 0 6.216 0.664 -0.453 0.00 0.00 C+0
ATOM 15 C 0 7.477 0.065 -0.367 0.00 0.00 C+0
ATOM 16 H 0 7.563 -0.970 -0.070 0.00 0.00 H+0
ATOM 17 O 0 8.475 0.709 -0.625 0.00 0.00 O+0
ATOM 18 C 0 -3.675 1.286 0.479 0.00 0.00 C+0
ATOM 19 C 0 -2.639 2.165 1.132 0.00 0.00 C+0
ATOM 20 C 0 -5.011 1.888 0.154 0.00 0.00 C+0
ATOM 21 C 0 -5.751 1.011 -0.857 0.00 0.00 C+0
ATOM 22 C 0 -5.724 -0.435 -0.357 0.00 0.00 C+0
ATOM 23 H 0 -4.556 -1.848 -2.369 0.00 0.00 H+0
ATOM 24 H 0 -3.949 -0.175 -2.410 0.00 0.00 H+0
ATOM 25 H 0 -2.861 -1.506 -1.947 0.00 0.00 H+0
ATOM 26 H 0 -3.194 -2.713 0.161 0.00 0.00 H+0
ATOM 27 H 0 -4.390 -2.154 1.355 0.00 0.00 H+0
ATOM 28 H 0 -4.930 -2.984 -0.123 0.00 0.00 H+0
ATOM 29 H 0 -1.948 -1.264 1.252 0.00 0.00 H+0
ATOM 30 H 0 -1.072 1.087 -0.523 0.00 0.00 H+0
ATOM 31 H 0 0.408 -2.384 0.672 0.00 0.00 H+0
ATOM 32 H 0 1.452 -1.459 1.778 0.00 0.00 H+0
ATOM 33 H 0 -0.308 -1.497 2.040 0.00 0.00 H+0
ATOM 34 H 0 1.321 1.294 -0.621 0.00 0.00 H+0
ATOM 35 H 0 2.803 -1.145 0.605 0.00 0.00 H+0
ATOM 36 H 0 3.721 1.482 -0.735 0.00 0.00 H+0
ATOM 37 H 0 6.292 -1.596 0.762 0.00 0.00 H+0
ATOM 38 H 0 4.716 -1.373 1.560 0.00 0.00 H+0
ATOM 39 H 0 4.802 -2.145 -0.042 0.00 0.00 H+0
ATOM 40 H 0 6.122 1.672 -0.831 0.00 0.00 H+0
ATOM 41 H 0 -2.064 2.682 0.364 0.00 0.00 H+0
ATOM 42 H 0 -3.134 2.897 1.770 0.00 0.00 H+0
ATOM 43 H 0 -1.970 1.551 1.735 0.00 0.00 H+0
ATOM 44 H 0 -5.603 1.966 1.066 0.00 0.00 H+0
ATOM 45 H 0 -4.866 2.883 -0.267 0.00 0.00 H+0
ATOM 46 H 0 -6.784 1.349 -0.948 0.00 0.00 H+0
ATOM 47 H 0 -5.256 1.073 -1.827 0.00 0.00 H+0
ATOM 48 H 0 -6.364 -1.053 -0.988 0.00 0.00 H+0
ATOM 49 H 0 -6.075 -0.473 0.674 0.00 0.00 H+0
CONECT 1 2 23 24 25 NONE 54
CONECT 2 1 22 3 4 NONE 55
CONECT 3 2 26 27 28 NONE 56
CONECT 4 2 5 18 0 NONE 57
CONECT 5 4 6 29 0 NONE 58
CONECT 6 5 7 30 0 NONE 59
CONECT 7 6 8 9 0 NONE 60
CONECT 8 7 31 32 33 NONE 61
CONECT 9 7 10 34 0 NONE 62
CONECT 10 9 11 35 0 NONE 63
CONECT 11 10 12 36 0 NONE 64
CONECT 12 11 13 14 0 NONE 65
CONECT 13 12 37 38 39 NONE 66
CONECT 14 12 15 40 0 NONE 67
CONECT 15 14 16 17 0 NONE 68
CONECT 17 15 0 0 0 NONE 69
CONECT 18 4 19 20 0 NONE 70
CONECT 19 18 41 42 43 NONE 71
CONECT 20 18 21 44 45 NONE 72
CONECT 21 20 22 46 47 NONE 73
CONECT 22 21 2 48 49 NONE 74
END</inlineContents>
</jmolApplet>
</jmol>

==='''A picture of roaccutane pill'''===
[[Image:Images.jpg]]

=='''reaction scheme'''==
[[Image:Synthesis.GIF]]

=='''Side effect and some precaution'''==
Isotretinoin causes birth defects if taken during pregnancy period.
This medicine may cause depression but rarely causes suicide attempts
Dry skin may be experienced. Dryness of the mucous membranes (lips and eyes).Disturbances in the composition of the blood may happen (increase plasma concentration).
Isotretinoin is used in combination with tetracycline-type antibiotics increases the pressure within the skull. For this reason, tetracycline antibiotics must not be taken with isotretinoin. An overdose, may cause changes in the structure of the bone. Roaccutane has a simmilar structure to vitamin A, therefore vitamin A supplements should therefore be avoided.

==References==
*[http://linkinghub.elsevier.com/retrieve/pii/S0190962298704384 ]- Journal of the American Academy of Dermatology, Volume 39, Issue 2, Pages S8-S12 U. Wiegand, R. Chou

===KIMCHI===

Roaccutane contains the active ingredient isotretinoin. This is a vitamin A derivative. Roaccutane is used to treat severe forms of acne (such as nodular orconglobate acne, or acne at risk of permanent scarring) which has not got better after other anti-acnetreatments, including oral antibiotics. Roaccutane treatment must be supervised by a dermatologist (a doctor specialised in the treatment of skin problems). Roaccutane may increase the levels of fats such as triglycerides or cholesterol in your blood. Roaccutane is teratogenic. This means that it is likely to damage an unborn baby. There is also an increased risk of miscarriage

===Physical and chemical properties===
Isotretinoin is a yellowish-orange crystalline powder with a melting point of about
175°C.
=====Solubility=====
Water: very sparingly soluble
Chloroform: soluble
Methylene chloride: soluble
Isopropanol: soluble
Polyethylene glycol soluble
Soy bean oil: less than 1 mg / 100 ml
Soybean oil is usually used as a suspension medium for Isotretinoin in soft gelatine capsule

[[Image: Isotretinoin.jpg]]

''Acne drug increases cholesterol levels''

Dermatology researches at the University of California, San Fransisco, have released the analysis of the effects caused by taking the drug isotretionin, the active ingredient in roaccutane.

The study involved 13,772 acne sufferers whose ages are between 13 and 50. They showed raised levels of triglyceride lipid esters in about 44% of the patients who used to have normal levels. 31% were reported for higher cholesterol levels. Anbormal results for liver function and cholesterol levels were also more common than expected.There was 11% increase in liver enzymes and abnormal liver tests. However, the aforementioned levels resumed to normal after discontinuing usage of the drug.

File:Isotretinoin.jpg

2006-12-07T11:49:27Z

Nha05:

File:Roaccutanediagram.jpg

2006-10-20T10:41:02Z

Nha05:

File:Roaccutane diagram.gif

2006-10-20T10:36:16Z

Nha05: