Phencyclidine

Phencyclidine (fen sye' kli deen) is an arylcyclohexylamine anesthetic that acts as a noncompetitive inhibitor of N-methyl-d-aspartate (NMDA) receptors in the brain.

Phencyclidine structure

Other names

Phencyclidine (fen sye' kli deen), commonly known as PCP, is an arylcyclohexylamine anesthetic that acts as a noncompetitive inhibitor of N-methyl-d-aspartate (NMDA) receptors in the brain.

History

PCP was initially developed as a human anesthetic but was later withdrawn due to its adverse psychological and behavioral effects. This article will discuss the clinical use, side effects, and recreational abuse of phencyclidine, as well as the development of related anesthetic agents.

Clinical Use and Indications

Phencyclidine infusions rapidly produce anesthesia and a unique cataleptic state characterized by profound analgesia, unresponsiveness, and amnesia, often with maintenance of muscle tone, involuntary movements, open eyes, and spontaneous breathing. This effect is called dissociative anesthesia, which can be associated with vivid hallucinations, agitation, and delirium during emergence. Due to these disturbing psychological and behavioral effects, phencyclidine (Sernyl) was withdrawn from human use in 1965. The drug continued to be available as a veterinary anesthetic (Sernylan) but was withdrawn from that use in 1978 in attempts to control its illicit availability.

Side Effects

Phencyclidine's dissociative effects led to its recreational abuse in the late 1960s and 1970s when it became a major drug of abuse, commonly known as "angel dust." When taken by mouth or inhaled (smoked) in doses of 1 to 10 mg, PCP leads to rapid onset of euphoria and feelings of omnipotence, superhuman strength, and social and sexual prowess. Chronic use of phencyclidine can be associated with severe violent and aggressive behavior and episodes of acute psychosis. Higher doses cause progressive confusion, disorientation, coma, and seizures, potentially leading to malignant hyperthermia, shock, rhabdomyolysis, renal failure, and sudden death. In recent years, increased awareness of its dangerous effects and limitations on its production have led to a decrease in the frequency (but not disappearance) of PCP abuse.

Development of Related Anesthetic Agents

Attempts to modify the tertiary amine structure of phencyclidine to develop a safer and more useful anesthetic agent led to the development of ketamine, another anesthetic with a similar mechanism of action. Ketamine shares some of PCP's dissociative effects, although to a lesser extent, and has a similar potential for abuse.

References

• Domino, E. F. (2010). Taming the Ketamine Tiger. Anesthesiology, 113(3), 678-684. doi:10.1097/ALN.0b013e3181ede0e7
• Giannini, A. J. (2000). Phencyclidine: An Update. Journal of Psychoactive Drugs, 32(4), 455-458. doi:10.1080/02791072.2000.10400241
• Jansen, K. L. (2001). A review of the nonmedical use of ketamine: Use, users and consequences. Journal of Psychoactive Drugs, 32(4), 419-433. doi:10.1080/02791072.2000.10400224
• Morris, H., & Wallach, J. (2014). From PCP to MXE: A comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis, 6(7-8), 614-632. doi:10.1002/dta.1620
• Olney, J. W., & Farber, N. B. (1995). NMDA antagonists as neurotherapeutic drugs, psychotogens, neurotoxins, and research tools for studying schizophrenia. Neuropsychopharmacology, 13(4), 335-345. doi:10.1016/0893-133X(95)00093-R
• White, P. F., & Trevor, A. J. (1989). Phencyclidine and ketamine: A view from the street. Anesthesiology, 71(5), 787-789. doi:10.1097/00000542-198911000-00023

Further Reading

• Gahlinger, P. M. (2004). Club drugs: MDMA, gamma-hydroxybutyrate (GHB), Rohypnol, and ketamine. American Family Physician, 69(11), 2619-2626. Retrieved from https://www.aafp.org/afp/2004/0601/p2619.html
• Krystal, J. H., Karper, L. P., Seibyl, J. P., Freeman, G. K., Delaney, R., Bremner, J. D., ... & Charney, D. S. (1994). Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Archives of General Psychiatry, 51(3), 199-214. doi:10.1001/archpsyc.1994.03950030035004
• Luby, E. D., Cohen, B. D., Rosenbaum, G., Gottlieb, J. S., & Kelley, R. (1959). Study of a new schizophrenomimetic drug; sernyl. AMA Archives of Neurology & Psychiatry, 81(3), 363-369. doi:10.1001/archneurpsyc.1959.02340150095011

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Recreational uses

Pharmacodynamics