Drug Dependence Liability of 4β-Methoxy-1-methyl-4α-phenyl-3α, 5α propanopiperidine hydrogen citrate (Azabicyclane) Tested in Rhesus Monkeys

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Morphine-like drug dependence liability of Azabicyclane, a new synthetic analgesic compound, was studied in rhesus monkeys. In gross behavior observation of acute CNS effects, the compound showed CNS depressant and toxic effects which were more similar to those of pethidine than to those of morphine. In the cross physical dependence test in monkeys, made physically dependent on morphine and then withdrawn, the compound did not support the dependence when it was substituted for morphine. Furthermore, the compound was antagonistic to morphine and precipitated withdrawal signs in morphine-dependent, non-withdrawn monkeys. However, when the compound was repeatedly administered to naive monkeys for a period of 31 days, severe grade withdrawal signs were observed in the levallorphan withdrawal and natural withdrawal tests. In cross intravenous self-administration of the compound, a CNS stimulant, and saline in self-administration conditioned monkeys, the compound showed obvious drug seeking behavior reinforcing effects at an appropriate unit dose range. When both naive and self-administration conditioned monkeys were allowed to self-administer the compound intravenously, without time or dose limitation, the animals voluntarily initiated self-administration, gradually increased the daily dose, and continued self-administration for longer than 6 weeks. The monkeys manifested marked CNS effects during this period. However, pethidine-like, psychotonaimetic effects were not observed. Therefore, although the pharmacological properties of Azabicyclane in connection with drug dependence, were not identical with those of pethidine, the potency of dependence liability, both physical and psychological, was similar to that of pethidine.
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Drug Dependence Liability of 4β-Methoxy-1-methyl-4α-phenyl-3α, 5α propanopiperidine hydrogen citrate (Azabicyclane) Tested in Rhesus Monkeys

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