View source for It:Scopolamine

==Scopolamine==

===Abstract===

As is common knowledge, scopolamine (systematic name (alpha)-(hydroxymethyl) benzeneacetic acid 9-methyl-3-oxa-9-azatricyclo [3.3.1.0 <sup>2,4</sup>] non-7-yl ester) was used during the Second World War as a 'truth drug' by the German Military and Intelligence (as many viewers and fans of 'The Guns of Navarone' would know). However, serving in this role, its success was limited, and scopolamine had (and indeed has) several other roles, neurological and otherwise, in human physiology and pharmacology. While it was used as a depressant (being an anticholigenic drug), it worked to mollify patients thanks to its sedative capabilities, thus making it easier to obtain 'blind' answers to question.

However, scopolamine is one of the drugs that is not technically synthesized chemically. Like insulin, scopolamine is produced (if required to be on a mass scale) by splicing the relevant gene responsible for its (enzyme) production onto the RNA sequence of a bacterium, usually of the ''E. coli'' family, or a derivative of it. Also, even then it needs the precursor to it to be present or produced: hyoscyamine.

In actuality, scopolamine is not all that common in the higher plants, one of the few plants capable of making it being ''Hyoscyamus niger''. In the case of ''H. niger'' the drug is produced in the branch roots. The reason behind the lack of frequency of the presence of scopolamine throughout the Solonaceae family of plants, is the lack of a particular gene. This gene is responsible for the production of the enzyme which catalyses the synthesis of scopolamine from hyoscyamine: hyoscyamine 6 [beta]-hydroxylase (often abbreviated to H6H).

Medically speaking though, the drug is rarely taken as its naturally occurring form. As with the majority of other drugs, it is taken as a salt analogue: scopolamine hydrochloride; or -methyl nitrate. Moreover, there are other analogues of scopolamine, such as atropine, though it is considered that the former has a greater central nervous systemic effect (hence its use in the treatment of motion sickness).

<u>'''Chemical Structure & Properties'''</u>

Scopolamine has the structure as below:

[[Image:Scopolamine.gif|thumb|left|Chemical Structure of Scopolamine]]

{| border="1"

| {{chembox header}} | Chemical & Biological Properties
|- 
| colspan="1" | Chemical Formula
| colspan="2" | C<sub>17</sub>H<sub>21</sub>NO<sub>4</sub>
|-
| colspan="1" | Melting Point
| colspan="2" | 381.2-390.2°C (as nitrate), 55°C (as hydrobromide trihydrate)
|-
| colspan="1" | Principle Indications 
| colspan="2" | excessive salivation, IBS, motion sickness
|-
| colspan="1" | Additional
| colspan="2" | colicky abdominal pain, sialorrhoea
|-
| colspan="1" | Mechanism
| colspan="2" | interference of ACh* in nerve impulses
|-
| colspan="1" | Biological Half-Life
| colspan="2" | approx. 9.5 hours in normal adult
|-
| colspan="1" | Solubility
| colspan="2" | highly soluble in both organic & inorganic solvents
|-
| 3D Structure
|<jmol>
<jmolApplet>
<size>325</size>
<color>white</color>
<script>zoom 100; cpk off;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>HEADER    CSD ENTRY XICKAV
ATOM      1  C1  MOL     1      17.518  11.060   2.578  1.00  0.00              
ATOM      2  N2  MOL     1      18.311  10.816   1.313  1.00  0.00              
ATOM      3  C3  MOL     1      17.739   9.837   0.345  1.00  0.00              
ATOM      4  C4  MOL     1      18.716  11.972   0.377  1.00  0.00              
ATOM      5  C5  MOL     1      18.794   9.982  -0.755  1.00  0.00              
ATOM      6  C6  MOL     1      16.350  10.296  -0.244  1.00  0.00              
ATOM      7  C7  MOL     1      19.631  11.141  -0.508  1.00  0.00              
ATOM      8  C8  MOL     1      17.583  12.505  -0.647  1.00  0.00              
ATOM      9  O9  MOL     1      20.100   9.876  -0.053  1.00  0.00              
ATOM     10  C10 MOL     1      16.253  11.893  -0.265  1.00  0.00              
ATOM     11  O11 MOL     1      15.129  12.413  -0.993  1.00  0.00              
ATOM     12  C12 MOL     1      13.942  12.104  -0.279  1.00  0.00              
ATOM     13  C13 MOL     1      12.622  12.698  -0.686  1.00  0.00              
ATOM     14  O14 MOL     1      14.003  11.453   0.779  1.00  0.00              
ATOM     15  C15 MOL     1      12.479  14.029   0.137  1.00  0.00              
ATOM     16  C16 MOL     1      11.432  11.762  -0.382  1.00  0.00              
ATOM     17  O17 MOL     1      11.300  14.783  -0.180  1.00  0.00              
ATOM     18  C18 MOL     1      10.201  12.231  -0.287  1.00  0.00              
ATOM     19  C19 MOL     1      11.669  10.316  -0.193  1.00  0.00              
ATOM     20  C20 MOL     1       9.076  11.341   0.015  1.00  0.00              
ATOM     21  C21 MOL     1      10.646   9.504   0.084  1.00  0.00              
ATOM     22  C22 MOL     1       9.293  10.040   0.196  1.00  0.00              
ATOM     23  H48 MOL     1      17.995  11.730   3.147  1.00  0.00              
ATOM     24  H50 MOL     1      17.423  10.202   3.083  1.00  0.00              
ATOM     25  H52 MOL     1      16.612  11.409   2.341  1.00  0.00              
ATOM     26  H54 MOL     1      17.572   8.929   0.730  1.00  0.00              
ATOM     27  H56 MOL     1      19.017  12.779   0.885  1.00  0.00              
ATOM     28  H58 MOL     1      18.340   9.606  -1.563  1.00  0.00              
ATOM     29  H60 MOL     1      16.257   9.948  -1.177  1.00  0.00              
ATOM     30  H62 MOL     1      15.614   9.929   0.325  1.00  0.00              
ATOM     31  H64 MOL     1      20.162  11.855  -0.966  1.00  0.00              
ATOM     32  H66 MOL     1      17.522  13.501  -0.592  1.00  0.00              
ATOM     33  H68 MOL     1      17.821  12.236  -1.580  1.00  0.00              
ATOM     34  H70 MOL     1      16.055  12.184   0.671  1.00  0.00              
ATOM     35  H72 MOL     1      12.607  12.851  -1.674  1.00  0.00              
ATOM     36  H74 MOL     1      12.452  13.797   1.109  1.00  0.00              
ATOM     37  H76 MOL     1      13.278  14.601  -0.048  1.00  0.00              
ATOM     38  H78 MOL     1      11.275  15.613   0.378  1.00  0.00              
ATOM     39  H80 MOL     1      10.033  13.207  -0.424  1.00  0.00              
ATOM     40  H82 MOL     1      12.595   9.946  -0.273  1.00  0.00              
ATOM     41  H84 MOL     1       8.150  11.710   0.085  1.00  0.00              
ATOM     42  H86 MOL     1      10.808   8.525   0.215  1.00  0.00              
ATOM     43  H88 MOL     1       8.529   9.430   0.408  1.00  0.00 
END</inlineContents>
</jmolApplet>
</jmol>
|-
|}
* ACh = acetylcholine, see below

[[Image:ACh.gif|thumb|left|Chemical Structure of Acetylcholine - ACh]]

==Biological Mechanism==

Scopolamine works by interfering with one of two sets of acetylcholine receptor sites which are the nicotinic (nAChR) and muscarinic (mAChR). The drug prevents the acetylcholine from binding with the latter (and nicotine induces a hypersensitivity at the former). This  Is done by the scopolamine itself binding to the receptor in the place of the ACh, thereby blocking it. Having done so, being attached, it creates no inducive effect for the nerve impulse to proceed, hence, the sedative effect, as chemical signals back and forth between brain and skeletal muscles are slowed down and/or prevented. As it acts more centrally to the spinal column and brain, it therefore dulls pain to the thorax and abdomen (the nerve arcs to the vital organs and those in close proximity being much shorter), thus its effectiveness in treating motion sickness and IBS (irritable bowel syndrome).

==Side effects==
Scopolamine has a lot of nerological side effects, and overdose on thedrug can lead to dillusion, delirium, paralysis, stupour and death. It also causes the pupils to dilate, and paralysis of the eye muscles in medium doses. The drug is also known to cause anisocoria, which is an effect characterised by an unequal size of the pupils and nausea. For this reason the effects of the drug can be confused with brain cancer, as these effects (nausea, and anisocoria) are also seen in patients with brain tumours.

==Uses==
Scopolamine was one of the drugs investigated in the 1950's for its 'truth drug' or mind control properties by the CIA and the British government. The investigations began on the back of intelligence obtained during the Cold War   suggesting that the Soviets had themselves obtained mind control capabilities. Other drugs tested by the intelligence agencies included but were not limited to LSD, mescaline, and quinuclidinyl benzyilate other chemical psycological and biological methods of mind control were also explored including for example sleep depravation.The test subjects would be given the drugs, then interrogated and their answeres recorded and analysed. Subjects would often be given the drugs without their knowledge and their reactions would be monitored. Scopolamine was abandoned as a possible truth drug because its hallucinogenic side effects meant that the answers obtained from subjects under the influence of the drug were were prone to distortion.

The drug has also found use as a 'date rape' drug, and also as an aid to robbery. In these cases the drug is usually administered to the victim by drugging the persons drink. It is used for this purpose because of its ability to cause amniesia in the victim, meaning that they forget events that happen prior to taking the drug.

As mentioned above the drug is also used in the treatment of motion sickness, and has become popular among divers for its use in the treatment of sea-sickness. It must though be taken with caution by divers as it has been found to cause pain in the eyes when divers reach depths of about 50 feet. This pain usually subsides if the diver rises to 40 feet or above.

==References==

Extended thanks to the following locations and parties for the use of their material:

[http://www.plantphysiol.org/cgi/content/abstract/105/2/483 Species-Dependent Expression of the H6H Gene in the Pericycle] Plant Physiology (Vol 105, 483-490): Molecular Biology & Gene Regulation - T. Kanegae, H. Kajiya, Y. Amano, T. Hashimoto and Y. Yamada

[http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD00616.txt  Scopolamine(APRD00616)] DrugBank

[http://www.drugs.com/pdr/scopolamine.html Scopolamine Drug Information] Drug Information Online (Prescription Drug Information for Consumers & Professionals)

[http://www.rense.com/general38/frug.htm Information on Scopolamine use in illegal activities]

also see [http://en.wikipedia.org/wiki/Acetylcholine Wikipedia's Acetylcholine]