Modulation of morphine-induced antinociception by ibogaine and noribogaine.

Ibogaine, a putative anti-addictive agent, and its active metabolite noribogaine modulate morphine's pain-killing (antinociceptive) effects in rats, depending on timing and dose. When given 19 hours before morphine, ibogaine significantly reduced morphine's antinociception, but had no effect alone. In contrast, co-administration of ibogaine (1-40 mg/kg) with morphine increased antinociception in a dose-dependent manner. Co-administration of noribogaine (40 mg/kg) with morphine also enhanced antinociception, while noribogaine pretreatment (19 hours) had no effect. The findings indicate that ibogaine acutely potentiates morphine antinociception, likely through noribogaine, but the delayed inhibitory effect after 19 hours is not explained by noribogaine.

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Abstract

The potential modulation of morphine antinociception by the putative anti-addictive agent ibogaine and its active metabolite (noribogaine) was investigated in rats with the radiant heat tail-flick test. Ibogaine pretreatment (40 mg/kg, i.p., 19 h) significantly decreased morphine (4 mg/kg, s.c.) antinociception, with no effects in the absence of morphine. However, co-administration of ibogaine (1-40 mg/kg, i.p.) and morphine (4 mg/kg, s.c.) exhibited a dose-dependent enhancement of morphine antinociception. Co-administration of noribogaine (40 mg/kg, i.p.) and morphine also resulted in an increase in morphine antinociception, while noribogaine pretreatment (19 h) had no effect on morphine antinociception. The results show that ibogaine acutely potentiates morphine antinociception and that noribogaine could be the active metabolite responsible for this effect. However, the inhibitory effects of a 19 h ibogaine pretreatment, which resemble ibogaine-induced inhibition of morphine's stimulant properties, cannot be accounted for by noribogaine.