APPETITE STIMULANT ACTIVITY OF 3-CARBOXY-10,11-DIHYDROXYPROHEPTADINE

  • 1 January 1976
    • journal article
    • research article
    • Vol. 223  (2) , 287-300
Abstract
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. [by mouth], 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 h 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 2 times more potent (protection against lethality in guinea-pigs exposed to an aerosol of histamine). As an anticholinergic in mice, CDC is > 13 times less active than cyproheptadine as a mydriatic agent and > 42 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.

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