Abuse potential and physical dependence liability studies with flupirtine maleate in laboratory animals

Flupirtine maleate is a centrally acting analgesic with a novel chemical structure and pharmacological profile. Because of its central mechanism(s) of action, flupirtine maleate was studied for physical dependence liability and abuse potential using the following four laboratory animal models: (1) mouse jumping test--jumping behaviour after narcotic antagonist challenge; (2) Hosoya test in rats--body weight reduction after drug withdrawal or narcotic antagonist challenge; (3) tolerance in mice--reduced analgesic activity after repeated dosing; and (4) self-administration in addicted Rhesus monkeys. Unlike the narcotic analgesic agents morphine and codeine, flupirtine maleate did not display evidence of physical dependence liability or abuse potential as measured by jumping behaviour in mice or body weight reduction in rats following repeated oral administration. Doses equal to or in excess of its analgesic dose were given for up to five weeks in these studies. No tolerance developed to the analgesic activity of flupirtine maleate in mice or rats dosed for up to 19 consecutive days. Finally, in morphine-dependent Rhesus monkeys, there was no difference in the rate of self-administration of flupirtine maleate when compared to the saline vehicle. Therefore, these results clearly show that flupirtine maleate, in animals, is without abuse potential and physical dependence liability.