Appetite stimulant activity of 3-carboxy-10,11-dihydrocyproheptadine.
The orexigenic and ancillary pharmacologic properties of 3-carboxy-10,11-dihydrocyproheptadine (CDC) were compared to those of cyproheptadine. The threshold dose, 0.0312 mg/kg p.o., of CDC for increasing food intake in the cat is similar to that of cyproheptadine, but CDC has a broader effective dose range, extending to 8 mg/kg p.o., compared with 1 mg/kg p.o. for cyproheptadine. Using an increase in food consumption of 20% or more as the criterion of a positive response, the dose effective in 50% of the animals was 0.35 mg/kg p.o. for both CDC and cyproheptadine. Both CDC and cyproheptadine possess a long duration of appetite-stimulant action, exceeding 18 hr following 0.5 mg/kg p.o. The ancillary pharmacologic properties of CDC are considerably reduced over those of cyproheptadine, except for antihistaminic activity, CDC being about two times more potent (protection against lethality in guinea-pigs exposed to an aeosol of histamine). As an anticholinergic in mice, CDC is greater than thirteen times less active than cyproheptadine as a mydriatic agent and greater than forty-two times less potent as an antagonist of oxotremorine-induced tremors. CDC retains only about 1/25 of the antiserotonin potency of the parent compound (inhibition of serotonin-elicited edema in the rat paw and 5-hydroxytryptophan provoked head twitch in rats). CDC reduced locomotor activity in rats to a significantly lesser degree than cyproheptadine. CDC thus is a more selective agent for the therapy of anorexia.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009184:Mydriatics; D010095:Oxotremorine / Q000037:antagonists & inhibitors; D010276:Parasympatholytics; D051381:Rats; D012702:Serotonin Antagonists; D013268:Stimulation, Chemical; D013997:Time Factors
D006634:Histamine H1 Antagonists; D009184:Mydriatics; D010276:Parasympatholytics; D012702:Serotonin Antagonists; D003533:Cyproheptadine; D010095:Oxotremorine