Ibogaine: A Potent Noncompetitive Blocker of GanglionidNeuronal Nicotinic Receptors

lbogaine noncompetitively blocked (IC,, 20 nM) “NaCI influx partially reversible in PC12 ceils. In viva, ibogaine at 10 mg/kg through ganglionic-type nicotinic receptor channels of rat completely blocked epibatidine-elicited antinociception in rheochromocytoma PC1 2 cells. The major metabolite O-desmice, a response that is mediated by central nicotinic receptor ;I-~ethylibogaine was 75fold less active, and O-t-butyl-O-deschannels. There was no significant blockade of the epibatidine methylibogaine was 20-fold less active. lbogaine was relatively response at 24 hr after the administration of 40 mg/kg ibogaine. weak as a blocker (IC,, 2000 r-r@ of the neuromuscular-type The blockade of nicotinic channels could contribute to the nicotinic receptor channels in human medulloblastoma TE671 antiaddictive properties of ibogaine. cells. The blockade of nicotinic responses by ibogaine was only