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- W105472392 abstract "ABSTRACT The effects of phencyclidine [PCP,.l-(l-phenylcyclohexyl)-piperidine] and two of its metabolites, l-(l-phenylcyclohexyl)-4-hydroxy piperidine (4-OH pip PCP) and l-(l-phenyl-4-hydroxycyclohexyl)-piperidine (4-OH cyclo PCP) were compared on rat locomotor activity and gross behavior in the dog. The two PCP metabolites produced some locomotor stimulation in the rat but were not as potent as PCP. The 4-OH pip PCP metabolite showed about 1/10 the activity of PCP; 4-OH cyclo PCP was even less potent in increasing rat locomotor activity. In the dog 1.0 mg/kg i.v. PCP produced a biphasic response with an initial phase of anesthesia and a subsequent phase of severe emergence delirium; in larger doses anesthesia with convulsions was observed. Equimolar doses to 1.0 mg/kg PCP of 4-OH pip PCP caused only slight ataxia and disorientation, while 4-OH cyclo PCP showed no effect. However, in ten times this dose 4-OH cyclo PCP was a frank cohvulsant, while 4-OH pip PCP was a less intense convulsant and produced some disorientation like PCP. Diazepam, diphenhydramine, droperidol, mecamylamine, physostigmine, 9-amino-l,2,3,4-tetrahydroacridine (THA), and scopolamine were tested as PCP antagonists when given prior to PCP in both the rat and dog. In the rat droperidol (0.32 mg/kg i.p.) and THA (10 mg/kg i.p.) significantly reduced the locomotor stimulant effects of PCP. In the dog these agents in a dose of 1.0 mg/kg i.v. as pretrea tment did not dramatically alter the PCP induced state. The plasma pharmacokinetics of PCP were determined in both the dog and monkey using gas chromatography-mass fragmentography in the electron impact mode (GC-MF-EI). In both species PCP (1 and 1.1 mg/kg i.v.) produced a complex exponential decline in the plasma levels with up to 2–3 phases. Compared to the monkey, the dog exhibited a pronounced emergence delirium during which time significant PCP plasma levels were detected. Very preliminary observations suggest that acidification of the urine in some human subjects may enhance urinary excretion. Carefully controlled animal studies are now being planned." @default.
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- W105472392 date "1978-01-01" @default.
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- W105472392 title "SOME ASPECTS OF THE PHARMACOLOGY OF PHENCYCLIDINE" @default.
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- W105472392 doi "https://doi.org/10.1016/b978-0-08-021938-7.50012-6" @default.
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