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Study on the dependence potential of -5-oxo-D-prolinepiperidinamide monohydrate in rhesus monkeys and rats



Study on the dependence potential of -5-oxo-D-prolinepiperidinamide monohydrate in rhesus monkeys and rats



Oyo Yakuri 55(2-3): 61-69, Feb -March



The dependence potential of (+)-5-OXO-D-prolinepiperidinamide monohydrate (NS-105) was assessed by four experiments in rhesus monkeys and rats. In gross behavioral observation for acute CNS effects with intravenous administration of NS-105 up to 128 mg/kg in 3 monkeys per dose, no specific effects were observed. In intravenous self-administration of NS-105 at 1, 4 and 16 mg/kg/infusion in 4 monkeys, no active intake was observed. Thereafter, NS-105 was forcibly administered at 4 mg/kg every 6 hr for 2 weeks but no active self-administration was observed during or after the forced administration period. In gross behavioral observation for CNS effects with intragastric administration of NS-105 up to 1,024 mg/kg in 4 rats per dose, no specific effects were observed except for slowed motor activity at 512 and 1,024 mg/kg in one rat each. Drug-admixed food was fed to 9 or 10 rats per dose group for 4 weeks in an attempt to produce physical dependence on NS-105. As a result, average daily drug intake (calculated once a week) ranged from 80 to 200 mg/kg in the NS-105 low dose group, 310 to 810 mg/kg in the NS-105 high dose group, and 180 to 540 mg/kg in the diazepam active control group. In the following 1-week withdrawal observation, food intake and body weight decreased and hyperirritability appeared in the diazepam group, peaking on withdrawal day 2, but neither withdrawal manifestation nor decrease of food intake or body weight was observed in either NS-105 group. The above results indicate that NS-105 may not possess either reinforcing effect (a crucial determinant of the drug's psychic dependence potential) or physical dependence potential.

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