ZIPEPROL - PRECLINICAL ASSESSMENT OF ABUSE POTENTIAL

Zipeprol was evaluated in a number of in vitro and in vivo assays pred ictive of stimulant, depressant, or opioid abuse potential. Zipeprol h ad affinity for mu and kappa opioid binding sites as well as sigma bin ding sites. However, it failed to exert opioid-like agonist actions in rodents, and did not attenuate withdrawal signs in morphine- or pento barbital-dependent rats. Zipeprol did not substitute for either amphet amine or pentobarbital in drug discrimination assays in rhesus monkeys . On the other hand, it suppressed morphine withdrawal signs in rhesus monkeys in two assays, and it acted as a quadazocine-sensitive reinfo rcer in monkeys trained to self-inject alfentanil. Zipeprol also acted as a reinforcer in monkeys trained to self-inject methohexital. In a dose range of 10-18 mg/kg, zipeprol induced convulsions in monkeys. Zi peprol appears to have abuse potential and a novel spectrum of action involving both opioid and non-opioid effects.