It07:Ketamine

Ketamine

Ketamine
General
Systematic name	2-(2-chlorophenyl)-2-methylamino-cyclohexan-1-one
Other names	Ketamine, K, Special K, Vitamin K
Molecular formula	C13H16ClNO
Molar mass	237.725gmol-1
CAS number	6740-88-1
Properties
Boiling point	266°C

Ketamine (2-(2-chlorophenyl)-2-methylamino-cyclohexan-1-one) is a dissasociative anaesthetic. It is widely used as a large animal tranquiliser in vetinary medicine, and a cheap, effective medicine for battlefield treatment in developing countries. It is also used recreationally, and is a class C illegal drug. The compound itself is enantiomeric, with the S-form being more physiologically active in humans.

History

Ketamine was developed as an alternative anaesthetic to PCP (Phencyclidine), after it was discovered that the latter caused hallucinations, mania, delirium and dissociation, as well as being neurotoxic. It was first synthesised in 1962 by Calvin Stevens, and was found in clinical (animal) trials as “the most promising of 200 PCP derivatives”. Human use, both medicinal and recreational was first reported in 1965, with the drug being officially released for clinical use in 1970. There was extensive reported use on American soldiers during the Vietnam war . In 1999, the drug was made a Schedule III controlled substance in the USA, primarily because of its applications as a date-rape drug. Following this, recreational use of ketamine has been made illegal in Hong Kong, Canada, and the UK (where it was made a class C drug in January 2006).

Medical Use

Contraindications: Alcohol Other sedatives Stimulants

Side effects: Severe: Detatchment from reality Sight impairment Loss of balance Distorted sense of time Cardiovascular: Partial depressant Gastrointestinal: Nausea Musculo skeletal: Relaxant High doses - Perceived paralysis Neurological: Analgesia Anasthesia Extended abuse - Memory loss Respiratory: Partial depressant/stimulant

In Humans

As a medicinal drug, ketamine is injected intravenously or intramuscularly, usually as a general anaesthetic. It may also be used in small doses as a local anaesthetic, however, where it counteracts pain caused by altered/damaged nerve pathways (neuropathic pain), or repetitive neuron firing, such as in spinal sensitisation. Because the doses are so low in these cases, the side effects can be managed easily with other medication (usually benzodiazapene). These pain relieving (analgesic) effects are much more effective when the ketamine is combined with low-dose opioids, such as codiene. This combination may be used in the treatment of migraine, and is effective in treating the pain associated with cancers.

Most available anaesthetics suppress the respiratory and circulatory systems, making them potentially dangerous to use on patients with an unknown medical history. Ketamine, however, stimulates these systems at anaesthetic doses, meaning less risk of heart failure, shock and asphyxiation during minor surgery.

Ketamine is also in clinical trials for use as an antidepressant, and as an aid in breaking addiction to other recreational drugs. Along with other drugs of its type, abuse produces symptoms which are used as a clinical model for research into schizophrenia.

In Animals

As a vetinary drug, ketamine is used on small animals in a similar capacity to that of humans, as well as as a continuous infusion analgesic to prevent the animal becoming aggressive due to pain. It is also used for pain management in large animals, particularly horses (hence the common colloquial description of the drug as a “horse tranquiliser” amongst those who are opposed to its use as a recreational drug.

Pharmacology and Neurological effects

Ketamine is a non-competitive antagonist of the NMDA receptor. NDMA receptors are present throughout the body, particularly the brain and spinal chord. They are particularly active during pain responses, hence the analgesic effect of ketamine blocking the receptors. Ketamine is synthesized as a racemic mix. The S-enantiomer has approximately four times the binding affinity to the NMDA receptor of the R-enantiomer. As it also has less side effects, it is sometimes preferred to the racemic mix for surgery.

As a recreational drug, it produces short-lived hallucinogenic effects, which are only visible against backgrounds such as darkness which have little sensory stimulation. Hallucinogenic effects only last around 15 minutes, with the associated analgesia lasting around 2 hours maximum. The “trip” brought on by recreational use of ketamine is described as:

Effects include changes in the perception of distances, relative scale, colour and durations/time, as well as a slowing of the visual system's ability to update what the user is seeing. There are reports of high-dosage users being able to see their surroundings in two sharp images, as if the brain is unable to merge the images each eye is sending. Speech often sounds unintelligible i.e. alogia, and auditory hallucinations may occur. At high doses sounds can be out of sync with the user's visual field. Ketamine at high doses produces a dissociative state, characterised by a sense of detachment from one's physical body and the external world[...] Some users may not remember this part of the experience after regaining consciousness, in the same way that a person may forget a dream. Owing to the role of the NMDA receptor in long-term potentiation, this may be due to disturbances in memory formation. The "re-integration" process is slow, and the user gradually becomes aware of surroundings. At first, users may not remember their own names, or even know that they are human, or what that means. Movement is extremely difficult, and a user may not be aware that he or she has a body at all.

—Ketamine, on Wikpedia

Ketamine’s effects on the brain have been shown to take place in the Hippocampus (long-term memory and spatial navigation centre) and prefrontal cortex (alertness and emotional response centre). This explains the side effect of memory loss, and the spatial hallucinations experienced by recreational users. The prefrontal cortex also regulates the areas of the brain responsible for consciousness, hence the detachment and anesthesia experienced by high-dose users.

Recreactional Use

Recreational use of Ketamine was first reported in 1965. It can be purchased over the counter in veterinary clinics in Mexico, where it is then diverted and sold for recreational use.

Ketamine can be insufflated, injected, or ingested dissolved in beverages. It can also be smoked, usually mixed with marijuana or tobacco. Oral administration produces a longer trip, but requires a larger dose. Injection is relatively uncommon, although possible. Smoking ketamine produces a faster high than other methods.