IBOGAINE AND NORIBOGAINE POTENTIATE THE INHIBITION OF ADENYLYL-CYCLASE ACTIVITY BY OPIOID AND 5-HT RECEPTORS

The effects of the putative anti-addictive compound ibogaine and its p rincipal metabolite, noribogaine, on adenylyl cyclase activity were de termined in various areas of the rat brain. Neither compound altered e ither basal or forskolin-stimulated adenylyl cyclase activities in the frontal cortex, midbrain or striatum. However, in all three brain are as the addition of ibogaine and noribogaine significantly enhanced inh ibition of adenylyl cyclase activity by a maximally effective concentr ation of morphine. Similarly, both compounds also potentiated the inhi bition of hippocampal adenylyl cyclase activity by a maximally effecti ve concentration of 5-hydroxytryptamine (5-HT). Although ibogaine appe ars to be more potent than noribogaine in augmenting opioid- and 5-HT- mediated inhibition of adenylyl cyclase activity, both compounds appea r to be of comparable efficacy. Neither compound, however, modified th e inhibitory action of the muscarinic acetylcholine agonist, carbachol , on adenylyl cyclase activity. The present data indicate that ibogain e and noribogaine cause a selective increase in receptor-mediated inhi bition of adenylyl cyclase activity. This potentiation may be involved in the pharmacological actions of these compounds.