Drug Dependence Liability Tests on 2- [β-pyridyl- (2″) -ethenyl] -3- (2′-methylphenyl) -quinazolinone- (4) (B169)

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Sedative-hypnotic type drug dependence liability of B 169, a new anticonvulsant, was studied in rhesus monkeys.<BR>In gross behavior observation of acute CNS effects by single oral doses of 500 and 1000 mg/kg, no meaningful effect was observed. At 2000 mg/kg, a slight decrease of spontaneous motor activity and of awareness to outer stimuli was observed one hour after administration. The monkeys, however, reacted normally to man without any impairment of motor function.<BR>In the cross physical dependence test in monkeys made, physically dependent on barbital and then withdrawn, the drug did not support the dependence when it was substituted for barbital at single oral doses of 1000 or 2000 mg/kg.<BR>When drug seeking behavior conditioned monkeys were allowed to self-administer the drug intragastrically by pressing a lever switch in the cage without time or dose limitation, none of the animals voluntarily ingested the drug. Since they did not initiate self-administration, timer-programmed forced infusion of the drug into the stomach was conducted at a dose regimen of 20 mg/kg/infusion every 6 hours for 2 weeks. Initiation of self-administration was still not observed during or after the programmed administration period. No withdrawal signs were observed at the termination of programmed administration.<BR>Thus, B169 was found to be dependence free.
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