THE PHARMACOLOGY OF 1-(1-PHENYLCYCLOHEXYL) PIPERIDINE-HCL

¹ Research Division, Parke, Davis & Company, Detroit, Michigan

1-(1-Phenylcyclohexyl)piperidine · HCl (PCP) acts principally on the central nervous system either by stimulation or by depression. Signs and symptoms vary considerably according to species of animals and dosage. Hyperactivity is more prominently observed in rats and mice; a certain degree of central depression, as manifested by the loss of muscle coordination of the limbs, may be detected also in these animals at all dose levels.

In pigeons, guinea pigs, hamsters, rabbits, cats, dogs and monkeys, PCP produces a quieting or calming effect at low doses and a cataleptoid response to general anesthesia at higher levels. Convulsive seizures occur in pigeons, guinea pigs, dogs and monkeys receiving PCP at doses higher than those for general anesthesia. On the other hand, convulsion or excitement is not clearly noticed in rabbits, cats, hamsters, frogs or fish with this compound at a very wide range of doses.

PCP is very effective in abolishing the electrically-or pentylenetetrazol-induced tonic-extensor seizures in mice, is slightly effective in suppressing caffeine-induced seizures but ineffective against those induced by strychnine.

PCP is not an analgesic agent at noncataleptoid or nonanesthetic dose levels. It possesses a local anesthetic activity approximitely one-half that of cocaine or twice that of procaine. It is devoid of an adrenergic blocking, a ganglionic blocking, an anticholinergic, an antihistaminic, or a depressant action on skeletal muscles.

Respiration and blood pressure are not markedly suppressed by PCP at anesthetic dosages; in fact the blood pressure is slightly elevated by the drug. At highly toxic dose levels, it will cause a suppression of respiration, hypotension and bradycardia. Such effects are transitory.

Neither the gastrointestinal motility nor the response of the nonpgregnant or the pregnant cat uteri to epinephrine are affected by PCP at neurotoxic dosages.

Some possible sites of action of PCP on the central nervous system are discussed from the standpoint of the pharmacological results presented.

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