Ibogaine: a potent noncompetitive blocker of ganglionic/neuronal nicotinic receptors.
Molecular pharmacology – January 01, 1997
Source: PubMed
Summary
Ibogaine effectively blocked sodium influx through specific nicotinic receptor channels, with an IC50 of around 20 nM in rat PC12 cells. Its major metabolite, O-des-methylibogaine, showed significantly reduced activity, being 75 times less effective. In human TE671 cells, ibogaine's blocking ability was weaker (IC50 approximately 2000 nM). In mice, a dose of 10 mg/kg completely inhibited pain relief from epibatidine, indicating potential anti-addictive properties. However, this effect was not sustained at 24 hours post-administration of a higher dose (40 mg/kg).
Abstract
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.