(+)- and (-)-3-Methoxycyproheptadine. A comparative evaluation of the antiserotonin, antihistaminic, anticholinergic, and orexigenic properties with cyproheptadine.
The synthesis and resolution of (+/-)-3-methoxycyproheptadine [(+/-)-4] are described. As a peripheral serotonin antagonist, (+/-)-4 was found to be one-half as potent as cyproheptadine (1b). The peripheral anticholinergic and antihistaminic activities as well as the orexigenic property of (+/-)-4 are less than those of 1b. A further comparison of the enantiomers (+)-4 and (-)-4 shows that all of the anticholinergic activity of (+/-)-4 resides solely in the dextrorotatory enantiomer, (+)-4, while the antiserotonin activity, which is similar to that of 1b, resides in the levorotatory enantiomer, (-)-4. Antihistaminic and orexigenic activity also resides in (-)-4 but these properties are reduced compared to those of 1b.
D000818:Animals; D001066:Appetite / Q000187:drug effects*; D002415:Cats; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000138:chemical synthesis*; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D010276:Parasympatholytics / Q000138:chemical synthesis*; D051381:Rats; D012702:Serotonin Antagonists / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D006633:Histamine Antagonists; D010276:Parasympatholytics; D012702:Serotonin Antagonists; D003533:Cyproheptadine