Physical dependence liability test of 4- (o-benzylphenoxy) -N-methylbutylamine hydrochloride (MCI-2016) in rats

Suzuki, T.; Imamaki, H.; Yoshii, T.; Ogawa, K.; Yanaura, S.

Journal of Toxicological Sciences 12(2): 147-163


ISSN/ISBN: 0388-1350
PMID: 3625810
DOI: 10.2131/jts.12.147
Accession: 040975357

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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 signs 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 signs. In a substitution test in either morphine or barbital dependent rats, no suppression of withdrawal signs or maintenance of dependence were observed by cross-administration of MCI-2016. In conclusion, MCI-2016 was considered to have no physical dependence potential.