Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses neither respiration nor heart rate. Ketamine is also simple to administer and highly tolerable compared to drugs with similar effects which are flammable, irritating, or even explosive. Ketamine is a novel compound, derived from PCP, created in pursuit of a safer anesthetic with similar characteristics. Ketamine is also used for acute pain management.At anesthetic doses, ketamine induces a state of "dissociative anesthesia", a trance-like state providing pain relief, sedation, and amnesia. The distinguishing features of ketamine anesthesia are preserved breathing and airway reflexes, stimulated heart function with increased blood pressure, and moderate bronchodilation. At lower, sub-anesthetic doses, ketamine is a promising agent for pain and treatment-resistant depression. However, the antidepressant action of a single administration of ketamine wanes with time. The long-term effects of repeated use are largely unknown, and are an area of active investigation.Liver and urinary toxicity have been reported among regular users of high doses of ketamine for recreational purposes. Ketamine is an NMDA receptor antagonist and that accounts for most of its actions except the antidepressive effect, the mechanism of which is a matter of much research and debate. Ketamine was first synthesized in 1962 and approved for use in the United States in 1970.
Some daily users reported withdrawal symptoms, primarily anxiety, shaking, sweating, and palpitations, following the attempts to stop. Cognitive deficits as well as increased dissociation and delusion symptoms were observed in frequent recreational users of ketamine. Interactions
Ketamine potentiates the sedative effects of propofol and  midazolam. Naltrexone potentiates psychotomimetic effects of a low dose of ketamine, while lamotrigine and nimodipine decrease them. Clonidine reduces the increase of salivation, heart-rate and blood-pressure during ketamine anesthesia and decreases the incidence of nightmares.Clinical observations suggest that benzodiazepines may diminish the antidepressant effects of ketamine. It appears most conventional antidepressants can be safely combined with ketamine. Pharmacology
Pharmacodynamics
Mechanism of action
Antagonism of the NMDA receptor is responsible for the anesthetic, analgesic, and psychotomimetic effects of ketamine. NMDA receptor antagonism results in analgesia by preventing central sensitization in dorsal horn neurons; in other words, ketamines actions interfere with pain transmission in the spinal cord.The mechanism of action of ketamine in alleviating depression is not well understood, and is an area of active investigation. Possible mechanisms include direct action on the NMDA receptor, downstream effects on regulators such as BDNF and mTOR, and effects of ketamines metabolites such as hydroxynorketamine. It is not clear whether NMDA receptor is solely responsible for this action or interactions with other receptors are also necessary. It is not also not clear whether ketamine alone is sufficient for the antidepressive action or its metabolites also are important.