Nicotinic agonists, antagonists, and modulators from natural sources.
1. Acetylcholine receptors were initially defined as nicotinic or muscarinic, based on selective activation by two natural products, nicotine and muscarine. Several further nicotinic agonists have been discovered from natural sources, including cytisine, anatoxin, ferruginine, anabaseine, epibatidine, and epiquinamide. These have provided lead structures for the design of a wide range of synthetic agents. 2. Natural sources have also provided competitive nicotinic antagonists, such as the Erythrina alkaloids, the tubocurarines, and methyllycaconitine. Noncompetitive antagonists, such as the histrionicotoxins, various izidines, decahydroquinolines, spiropyrrolizidine oximes, pseudophrynamines, ibogaine, strychnine, cocaine, and sparteine have come from natural sources. Finally, galanthamine, codeine, and ivermectin represent positive modulators of nicotinic function, derived from natural sources. 3. Clearly, research on acetylcholine receptors and functions has been dependent on key natural products and the synthetic agents that they inspired.
Daly
John W
JW
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, Maryland 20892, USA. jdaly@nih.gov
D000818:Animals; D006801:Humans; D018722:Nicotinic Agonists / Q000737:chemistry* / Q000302:isolation & purification; D018733:Nicotinic Antagonists / Q000737:chemistry* / Q000302:isolation & purification; D010944:Plants / Q000737:chemistry*; D014118:Toxins, Biological / Q000737:chemistry* / Q000302:isolation & purification; D014688:Venoms / Q000737:chemistry* / Q000302:isolation & purification
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D014118:Toxins, Biological; D014688:Venoms