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

European Journal of Pharmacology
R A Rabin, J C Winter

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.

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Citations

Nov 10, 2013·PloS One·Tamara AntonioKenneth Alper
Nov 22, 2007·Journal of Ethnopharmacology·Kenneth R AlperCharles D Kaplan
Jan 25, 2012·Journal of Forensic Sciences·Kenneth R AlperJames R Gill
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paul CummingChantal Martin-Soelch

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