Ibogaine: A Potent Noncompetitive Blocker of Ganglionic/Neuronal Nicotinic Receptors
1997; American Society for Pharmacology and Experimental Therapeutics; Volume: 51; Issue: 1 Linguagem: Inglês
10.1124/mol.51.1.1
ISSN1521-0111
AutoresBarbara Badio, William L. Padgett, John W. Daly,
Tópico(s)Ion channel regulation and function
ResumoIbogaine noncompetitively blocked (IC 50 ∼ 20 nm) 22 NaCl influx through ganglionic-type nicotinic receptor channels of rat pheochromocytoma PC12 cells. The major metabolite O -desmethylibogaine was 75-fold less active, and O - t -butyl- O -desmethylibogaine was 20-fold less active. Ibogaine was relatively weak as a blocker (IC 50 ∼ 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.
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