Anesthetics, dissociative

The benzodiazepines were among the first class of drugs developed as a result of targeted modem drug discovery techniques. Drugs used specifically to treat psychological problems and mental illnesses are relatively new compared 

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Dissociative anesthetic is a term applied to phencyclidine and ketamine which induce a peculiar subjective state of dissociation from the environment, together with sedation, immobility, amnesia, analgesia, and ultimately coma. 

For many years it was believed that the brain mechanisms underlying the effects of psychedelic hallucinogens and dissociative anesthetics were separate and distinct. Indeed, there has been considerable debate about which represents the best drag model of schizophrenia. However, recent data show that the two classes of psychotomimetic drags share a common final pathway involving an increase in the release of the excitatory neurotransmitter glutamate. 

Psychotomimetic Drugs. Figure 2 Chemical structures of the dissociative anesthetics phencyclidine (PCP) and ketamine. Both are arylcycloalkylamine derivatives that are open channel blockers of the NMDA channel. 

Phencyclidine (l-[l-phenylcyclohexyl] piperidine, PCP) was originally developed as an intravenous anesthetic in the 1950s. Used for this indication, it causes a trance-like state without loss of consciousness and was hence classified as a dissociative anesthetic. However, it was soon withdrawn from human use because it produced unpleasant hallucinations, agitation, and delirium. The product was later used in veterinary medicine. Ketamine, a chemically closely related substance, was developed to replace PCP and is stiU in use as a dissociative anesthetic in children. Ketamine is less potent than PCP, and its effects are of shorter duration. However, it may also cause hallucinations (see the section on ketamine in Chapter 7, Club Drugs ). Much of the ketamine sold on the street (special K, cat Valium) has been diverted from veterinarians offices. 

Phencyclidine (PCP), a dissociative anesthetic agent, which is subject to abuse, produces behavioral effects in man that frequently resemble schizophrenia (Luisada 1978). Manifestations of persistent psychopathology frequently remain after the acute effects of PCP have diminished. With PCP, subjects may display autistic and delusional thinking typical of schizophrenics (Luby et al. 1959). A more striking link between schizophrenia and PCP comes from observations of cases in which PCP was given to hospitalized schizophrenics (Luisada 1978). After receiving PCP, these patients showed extreme exacerbation of their psychoses the reaction persisted for up to 6 weeks. By contrast, LSD produced no more severe effects in schizophrenics than in normal subjects. 

Hypofunction of NMDA receptors may contribute to the endophenotype of schizophrenia. The hypothesis that hypofunction of a subpopulation of NMDA receptors contributes to the pathophysiology of schizophrenia has gained considerable support over the last decade (see Fig. 54-1). The dissociative anesthetics including phencyclidine (PCP) and ketamine when introduced clinically 40 years ago were noted to produce a syndrome that was difficult to distinguish from schizophrenia. These agents act as noncompetitive open-channel blockers of the NMDA receptor. 

Actions Dissociative anesthetic gas Effects Dizziness, suffocation d/t inhalation device (ie, garbage bag, balloon)... 

Domino EF, Chodoff P, Corssen G (1965) Pharmacologic effects of Cl-581, a new dissociative anesthetic, in man. Clin Pharmacol Ther 6 279-291 Doraiswamy PM (2002) Non-cholinergic strategies for treating and preventing Alzheimer s disease. CNS Drugs 16 811-824... 

Some 30 phencyclldlne-llke compounds are known to produce psychophysical effects resembling those of SNA. Of these, ketamine (Ketalar, Ketaject), a chlorophenyl methylamlnocyclohexanone, is currently used fairly widely as a dissociative anesthetic In humans. Therefore, Its use can provide clinical information about undeslred effects of single doses of the phencyclidine series. 

Tolerance to dissociative anesthetics does develop. Psychological dependence is greater than physical dependence, although withdrawal symptoms may last for several weeks and include diarrhea, chills, tremor, anxiety, depression, and irritability. Prolonged use of PCP may induce permanent learning disabilities, amnesia, depression, and antisocial behavior. 

PCP and ketamine are dissociative anesthetics. They can induce analgesia without loss of consciousness. The individual appears awake but will not remember the experience, and vital signs such as respiration and heart rate are not impaired. The drugs distort perceptions of sight and sound, and produce feelings of detachment and dissociation from the environment and self. Persons abusing PCP exhibit very bizarre behavior and may become violent. 

Dissociative anesthetic A drug that produces significant analgesia while the patient remains awake and feels removed from the surrounding environment, without depressing vital signs. 

Ketamine, a unique dissociate anesthetic with analgesic properties, does not produce its effects via facilitation of GABAa... 

STREET NAMES K, ket, quick, lady K, special K, vitamin K DRUG CLASSIFICATIONS Schedule III, dissociative anesthetic... 

Ketamine is chemically related to other dissociative anesthetics, including dextromethorphan (DXM), found in some over-the-counter cough syrups, and nitrous oxide (often called whippets ). Ketamine also shares a close chemical kinship to the prescriptives tiletamine and memantine. Tiletamine is used in combination with zolazepam as a veterinary anesthetic under the brand names Zoletic and Telazol. 

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