Abstract
Ibogaine noncompetitively blocked (IC50 ∼ 20 nm) 22NaCl influx through ganglionic-type nicotinic receptor channels of rat pheochromocytoma PC12 cells. The major metabolite O-desmethylibogaine was 75-fold less active, andO-t-butyl-O-desmethylibogaine was 20-fold less active. Ibogaine was relatively weak as a blocker (IC50 ∼ 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.
- The American Society for Pharmacology and Experimental Therapeutics
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