Ibogaine: a potent noncompetitive blocker of ganglionic/neuronal nicotinic receptors.

Ibogaine blocks a specific type of nicotinic receptor channel (ganglionic type) in rat cells, with an IC50 around 20 nM. Its main metabolite, O-des-methylibogaine, is 75 times less potent, and a modified version is 20 times less potent. Ibogaine is much weaker at blocking neuromuscular-type nicotinic receptors. The blockade in rat cells is only partially reversible. In mice, a 10 mg/kg dose of ibogaine completely blocks pain relief caused by epibatidine, which acts through central nicotinic receptors. This effect is gone 24 hours after a 40 mg/kg dose. Blocking these channels may contribute to ibogaine's anti-addictive properties.

Study at a glance

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.