The effect of acute phencyclidine administration on cyclopropane requirement (MAC) in rats.

The effect of acute administration of phencyclidine (PCP) on the anesthetic requirement (MAC) was studied in rats. Rats were anesthetized with cyclopropane and MAC determinations were made by the tail-clamp technique. PCP, 2 or 4 mg/kg, subcutaneously, produced a 32 and 42 per cent decrease, respectively, in cyclopropane MAC. The PCP-induced decrease in MAC was not altered by naloxone treatment indicating that an interaction of PCP with opiate mechanisms is unlikely. Central monoamine depletion with reserpine decreased cyclopropane MAC by 20 per cent. In these monoamine-depleted rats, 4 mg/kg PCP produced a further reduction in MAC of 22 per cent. In rats almost totally depleted of catecholamines by pretreatment with reserpine and alpha-methyl-p-tyrosine, a marked (43 per cent) decrease in MAC was observed. The administration of 2 mg/kg PCP, in these catecholamine-depleted rats produced an additional 10 per cent decrease in MAC for a total reduction in MAC of 53 per cent. The effect of PCP in the monoamine- and catecholamine-depleted rats indicates that while an effect on central monoamines may play a part in the mechanism of action of PCP, it is not the sole mode of action of the drug. In patients intoxicated with PCP there is a significant potential for anesthetic overdose as their anesthetic requirement may be much less than would be expected in the nonintoxicated state.