Pharmacologic Effects of Ci-581, a New Dissociative Anesthetic, in Man

Abstract

Pharmacologic actions of CI-581, a chemical derivative of phencyclidine, were determined in 20 volunteers from a prison population. The results indicate that this drug is an effective analgesic and anesthetic agent in doses of 1.0 to 2.0 mg. per kilogram. With intravenous administration the onset of action is within 1 minute and the effects last for about 5 to 10 minutes, depending on dosage level and individual variation. No tachyphylaxis was evident on repeat doses. Respiratory depression was slight and transient. Hypertension, tachycardia, and psychic changes are undesirable characteristics of the drug. Whether these can be modified by preanesthetic medication was not determined in this study. Recovery from analgesia and coma usually took place within 10 minutes, although from electroencephalographic evidence it may be assumed that subiects were not completely normal until after 1 to 2 hours. No evidence of liver 01' kidney toxicity was obtained. CI-581 produces pharmacologic effects similar to those reported for phencyclidine, but of shorter duration. The drug deserves further pharmacologic and clinical trials. It is proposed that the words "dissociative anesthetic" be used to describe the mental state produced by this drug.The remarkable analgesic and anesthetic properties of phencyclidine have stimulated a search for derivatives that would offer the same benefits with less psychotomimetic effects. 3 Recent studies in laboratory animals by McCarthy and co-workers7 indicate that such an agent might be found in CI-581, a chemical derivative of phencycli-dine, with the formula, 2-( o-chlorophenyl)-2-methylamino cyclohexanone HCI (Fig. 1). CI-581 produced immobilization and/or general anesthesia in a variety of animals and in a broad range of dosages. Although this compound is less potent on a milligram per kilogram basis than phencyclidine, its central depressant action is significant with much less central excitatory effects. Moreover, CI-581 has a shorter duration of action which should allow greater controlability in clinical use.

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