PHYSICAL DEPENDENCE LIABILITY TEST OF 4-(o-BENZYLPHENOXY)-N-METHYLBUTYLAMINE HYDROCHLORIDE (MCI-2016) IN RATS

Abstract

An acute administration of MCI-2016 at the doses of 30, 100 and 300 mg/kg (p.o.), and 10, 20 and 30 mg/kg (i.p.) produced a slight CNS depression in rats, such as, sedation, ptosis, decrease in motor activity and systemic muscle relaxation. In a direct physical dependence test, rats were fed the MCI-2016-admixed food together with drinking water ad libitum for 24 hours daily for 51-71 days (mean MCI-2016 intake 29.9-210.7 mg/kg/day), on the gradedly increased dosage schedule with a dosage level of 0.25 and 0.5 mg/g food to 4 mg/g food. In a natural withdrawal following administration of MCI-2016, no significant withdrawal sings were observed in any group. In a naloxone-precipitation test the rats that were treated with MCI-2016-admixed food did not show any withdrawal sings. In a substitution test in either morphine or barbital dependent rats, no suppression of withdrawal sings or maintenance of dependence were observed by cross-administration of MCI-2016. In conclusion, MCI-2016 was considered to have no physical dependence potential.