Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine
Journal of Pharmacology and Experimental Therapeutics January 1, 1999 John Denis Fryer, Ronald J. Lukas 283 citations
Bupropion, phencyclidine, and ibogaine each block two types of human nicotinic acetylcholine receptors (nAChR): the muscle-type (alpha1 beta gamma delta) and the ganglionic type (alpha3 beta4 alpha5+/-beta2). The blockade occurs at low to intermediate micromolar concentrations and cannot be overcome by increasing the amount of agonist, indicating noncompetitive inhibition. These findings suggest that nAChR are targets for diverse substances of abuse and for agents used in antiaddiction and smoking cessation strategies, and that nAChR may play underappreciated roles in depression and as targets for clinically useful antidepressants.