Effects of ibogaine and noribogaine on the antinociceptive action of mu-, delta- and kappa-opioid receptor agonists in mice.

Ibogaine, an alkaloid isolated from the bark of the African shrub, Tabernanthe iboga, has been claimed to decrease the self-administration of drugs of abuse like morphine, cocaine and alcohol. To determine whether these effects are mediated via opioid receptor systems, the effects of ibogaine and its metabolite, noribogaine on the antinociceptive actions of morphine, U-50,488H and [D-Pen2,D-Pen5]enkephalin (DPDPE) which are mu- kappa- and delta-opioid receptor agonists, respectively, were determined in male Swiss-Webster mice. Administration of morphine (7 or 10 mg/kg, s.c.), U-50,488H (15 or 25 mg/kg, i.p.) or DPDPE (10 microg/mouse, i.c.v.) produced antinociception in mice as measured by the tail-flick test. Ibogaine (10, 20 or 40 mg/kg, i.p.) by itself did not alter the tail-flick latency. The same doses of ibogaine injected 10 min before the opioid drugs did not modify the antinociceptive actions of morphine, U-50,488H or DPDPE. Ibogaine administered 4 h or 24 h prior to morphine injection did not modify the antinociceptive action of the latter. A dose of 40 mg/kg (i.p.) of noribogaine enhanced the antinociceptive activity of morphine (10 mg/kg, s.c.). Similarly, the doses of 40 and 80 mg/kg of noribogaine enhanced the antinociception produced by a smaller dose of morphine (5 mg/kg, s.c.). However, antinociception induced by U-50,488H and DPDPE was not modified by noribogaine (10-40 mg/kg). It is concluded that ibogaine, which has been suggested to decrease the self-administration of cocaine and opiates like heroin in humans, does not produce such an action by interacting directly with multiple opioid receptors. However, the metabolite of ibogaine enhances the antinociception of morphine but not of U-50,488H or DPDPE. Thus, in vivo evidence has been provided for the possible interaction of ibogaine with mu-opioid receptor following its metabolism to noribogaine.