Ibogaine and noribogaine potentiate the inhibition of adenylyl cyclase activity by opioid and 5-HT receptors.

Ibogaine and its metabolite noribogaine do not directly alter adenylyl cyclase activity in the rat brain, but they enhance the inhibition of this enzyme caused by morphine and serotonin. In the frontal cortex, midbrain, and striatum, both compounds amplified morphine's effect; in the hippocampus, they boosted serotonin's effect. Ibogaine was more potent than noribogaine, but both were equally effective. The compounds did not affect inhibition by the muscarinic agonist carbachol. This selective potentiation of receptor-mediated inhibition may contribute to ibogaine's pharmacological actions.

Study at a glance

Abstract

The effects of the putative anti-addictive compound ibogaine and its principal metabolite, noribogaine, on adenylyl cyclase activity were determined in various areas of the rat brain. Neither compound altered either basal or forskolin-stimulated adenylyl cyclase activities in the frontal cortex, midbrain or striatum. However, in all three brain areas the addition of ibogaine and noribogaine significantly enhanced inhibition of adenylyl cyclase activity by a maximally effective concentration of morphine. Similarly, both compounds also potentiated the inhibition of hippocampal adenylyl cyclase activity by a maximally effective concentration of 5-hydroxytryptamine (5-HT). Although ibogaine appears to be more potent than noribogaine in augmenting opioid- and 5-HT-mediated inhibition of adenylyl cyclase activity, both compounds appear to be of comparable efficacy. Neither compound, however, modified the inhibitory action of the muscarinic acetylcholine agonist, carbachol, on adenylyl cyclase activity. The present data indicate that ibogaine and noribogaine cause a selective increase in receptor-mediated inhibition of adenylyl cyclase activity. This potentiation may be involved in the pharmacological actions of these compounds.