A single administration of
ifenprodil at the doses of 100, 200 and 400 mg/kg (p.o.), and 50 and 100 mg/kg (i.m.) produced a moderate CNS depression in rats, such as, sedation, ptosis, systemic muscle relaxation and decrease in motor activity. These symptoms appeared dose-dependently and persisted for about 4 hours following administration. In a direct physical dependence test, 5 groups of rats were fed the
ifenprodil-admixed food together with
drinking water ad libitum for 24 hours daily for 53 approximately 103 days (mean
ifenprodil intake, 43--240 mg/kg/day), on the gradedly increased dosage schedule with a dosage level of 0.5 vs. 1 mg/g food to 4 mg/g food. In the natural withdrawal following administration, no significant withdrawal signs were observed in any group. In a substitution test either for
phenobarbital or
morphine, no suppression of withdrawal signs during the period of cross-administration of
ifenprodil and no maintenance of dependence were observed. In a physical dependence-producing test, the rats fed
ifenprodil never manifested withdrawal signs such as
diarrhea, "wet shakes", sudden loss of
body weight as in the
levallorphan precipitation test.
Ifenprodil apparently has no physical dependence liability.