Ibogaine: a potent noncompetitive blocker of ganglionic/neuronal nicotinic receptors.
Ibogaine noncompetitively blocked (IC50 approximately 20 nM) 22NaCl influx through ganglionic-type nicotinic receptor channels of rat pheochromocytoma PC12 cells. The major metabolite O-des-methylibogaine was 75-fold less active, and O-t-butyl-O-des-methylibogaine was 20-fold less active. Ibogaine was relatively weak as a blocker (IC50 approximately 2000 nM) of the neuromuscular-type nicotinic receptor channels in human medulloblastoma TE671 cells. The blockade of nicotinic responses by ibogaine was only partially reversible in PC12 cells. In vivo, ibogaine at 10 mg/kg completely blocked epibatidine-elicited antinociception in mice, a response that is mediated by central nicotinic receptor channels. There was no significant blockade of the epibatidine response at 24 hr after the administration of 40 mg/kg ibogaine. The blockade of nicotinic channels could contribute to the antiaddictive properties of ibogaine.
Badio
B
B
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0820, USA.
Padgett
W L
WL
Daly
J W
JW
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005730:Ganglionic Blockers / Q000494:pharmacology*; D006801:Humans; D007050:Ibogaine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000188:drug therapy; D016716:PC12 Cells; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D005730:Ganglionic Blockers; D018733:Nicotinic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007050:Ibogaine; D002217:Carbachol; D004298:Dopamine