77-10-1

Anesthetic.

ChEBI: A member of the class of piperidines that is piperidine in which the nitrogen is substituted with a 1-phenylcyclohexyl group. Formerly used as an anaesthetic agent, it exhibits both hallucinogenic and neurotoxic effects.

Sernylan (Parke-Davis).

Phencyclidine was introduced as a dissociative anestheticfor animals. Its close structural relative ketamine is still soused and may be used in humans. In humans,PCP produces a sense of intoxication, hallucinogenic experiencesnot unlike those produced by the anticholinergic hallucinogens,and often, amnesia.
The drug affects many systems, including those of NE,DA, and 5-HT. It has been proposed that PCP (and certainother psychotomimetics) produces a unique pattern of activationof ventral tegumental area dopaminergic neurons.Itblocks glutaminergic N-methyl-D-aspartate receptors.Thisaction is the basis for many of its CNS effects. PCP itself appearsto be the active agent. The psychotic state produced bythis drug is also cited as a better model than amphetaminepsychosis for the psychotic state of schizophrenia.

This piperidine (FWfree-base = 243.39 g/mol; CAS 77-10-1: Symbol: PCP), commonly known as Angel Dust and systematically as 1- (1- phenylcyclohexyl) piperidine, is a NMDA (N-methyl-D-aspartate) antagonist, psychostimulant, s receptor agonist, and frequent drug of abuse (2-5). Formerly used as a veterinary anesthetic and briefly as a general anesthetic in humans, phencyclidine is also a powerful hallucinogen. Mode of Action: NMDA receptors play important roles in mediating excitatory neurotransmission and are preferentially inhibited by some general anesthetics. Phencyclidine is similar to ketamine in structure and in many of its effects; both produce a dissociative state (See Ketamine). Phencyclidine inhibits activation of NMDA receptors (3-5), inducing schizophrenia-like symptoms in healthy individuals and exacerbating pre-existing symptoms in patients with schizophrenia. PCP behavioral effects are strongly dose- dependent: low doses (3-5 mg) produce intoxication (characteristics: numbness in the extremities, staggering or unsteady gait, slurred speech, and bloodshot eyes); moderate doses (e.g., 5–10 mg intranasal or 0.01–0.02 mg/kg IM or IV) produce analgesia and anesthesia; and high doses often lead to convulsions. Pharmacokinetics & Metabolism: PCP is well absorbed by all routes of administration, but, in cigarette smoke, about half is converted to an inactive thermal degradation product. PCP is highly lipid- soluble, accouting for its tendency to concentrate in fat and brain tissue. The plasma binding of PCP is 65%, and its t1/2 ranges from 7-46 hours, with a 21-hour average. PCP is extensively metabolized to inactive metabolites by a variety of metabolic routes. Benzodiazepines decrease PCP’s hypertensive effects and reverse seizure activity. PCP is also an inhibitor of a number of cytochrome P450 systems and a suicide inhibitor of nitric-oxide synthase . However, the inhibition of nitric-oxide synthase is not related to the psychotomimetic action of phencyclidine. Target (s) : Ca2+-dependent ATPase; CYP2B1; K+ channels, ATP-sensitive; nitric-oxide synthase; and NMDA-receptor channel. Phencyclidine is a powerful, noncompetitive inhibitor of the nicotinic acetylcholine receptor in a sympathetic nerve cell line, PC-12. In the presence of 1 mM carbamoylcholine, the rate of the receptor-controlled influx of 22Na+ is reduced by a factor of 2 by 0.7 μM phencyclidine.

When mice and rats are administered phencyclidine intraperitoneally, several hydroxylated metabolites are identified in the urine. A new metabolite, 1-phenyl-1- (1-piperidinyl-3-ol)cyclohexane, is identified in the urine and liver microsomal preparations.