Drug Dependence Liability of Calcium N-2-ethylhexyl-β-oxybutyramide semisuccinate (M-2) Tested in Rhesus Monkeys

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Barbiturate-like drug dependence liability of Calcium N-2-ethylhexyl-β-oxybutyramide semisuccinate (M-2), a new synthetic sedative-hypnotic agent, was studied in rhesus monkeys.<BR>In gross behavior observation of acute CNS effects, the compound did not show as strong CNS depressant effects in monkeys as it had in small animals.<BR>A physical dependence producing test was conducted by oral administration of the compound 4 times a day, for 4 weeks at dose levels of 100, 200, or 400 mg/kg/day, with 2 naive monkeys for each dose level. At the end of 4 weeks, administration was terminated and a withdrawal test was conducted for 5 days. No meaningful withdrawal signs were observed. On the other hand, oral administration of barbital for 4 weeks produced intermediate to severe grade withdrawal signs in other monkeys.<BR>In cross intravenous self-administration of M-2, a CNS stimulant and saline in self-administration conditioned monkeys, the compound did not show drug seeking behavior reinforcing effects at unit doses of 0.25, 1.0, and 4.0 mg/kg/inj..<BR>Because of the lack of CNS depressant effects, ability of producing physical dependence and drug seeking behavior reinforcing effects, the potency of dependence liability of M-2 was concluded as practically none.
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