Ibogaine and noribogaine potentiate the inhibition of adenylyl cyclase activity by opioid and 5-HT receptors.
European journal of pharmacology – December 05, 1996
Source: PubMed
Summary
Ibogaine and its metabolite noribogaine significantly enhance the inhibition of adenylyl cyclase activity by morphine and serotonin in rat brain regions, suggesting their potential role in addiction treatment. In experiments involving various brain areas, both compounds increased the inhibitory effects of morphine and 5-hydroxytryptamine (5-HT) on adenylyl cyclase without altering baseline activity. While ibogaine showed greater potency than noribogaine, both exhibited similar efficacy. Notably, neither compound affected the action of carbachol, indicating a selective mechanism of action.
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.