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.

PCP acts as a biocide through its ability to uncouple mitochondrial oxidative phosphorylation.

Poison by intraperitoneal route. Experimental reproductive effects. Caution: This is a controlled substance (depressant) listed in the U.S. Code of Federal Regulations, Title 21 Part 1308.12 (1985). The ethylamine, pyrrolidine and thiophene analogs are l

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.

Pentachlorophenolwas metabolized in rats by conjugation with glucuronic acid and eliminated as the glucuronide. P450 catalyzed oxidative dechlorination also occurred to form tetrachlorohydroquinone, and this was conjugated to form a monoglucuronide representing 27% of the dose administered. Other metabolites have been reported, including isomeric tetrachlorophenols, tetrachlorocatechol and tetrachlororesorcinol. Trace amounts of benzoquinones were also noted.
Metabolites in female rats were tetrachloromonophenols, diphenols, and hydroquinones.

The toxicology has been addressed in a recent risk assessment (119). Acutely, pentachlorophenol was reported to have LD₅₀ values in the rat of 12 mg/kg (inhalation) and 146 mg/kg (M)–175 mg/kg (F) by oral gavage. More detailed studies of the toxicology of pentachlorophenol have been compromised by the toxicity of impurities present in most of the earlier samples used in the evaluation process.