Effects of indorenate on food intake: a comparison with fenfluramine and amphetamine

Indorenate (TR3369, 5-methoxytryptamine b-methylcarboxylate HCl) is a 5-HT₁-like receptor agonist with hypotensive activity. Here, we describe that indorenate also decreases food intake (ED₅₀ 26.1 mg/kg) without an appreciable effect in water intake (the estimated ED₅₀ for water was 589.8 mg/kg). The anorectic activity of indorenate was compared to the effects of amphetamine and other serotonin agonists; the effect of indorenate was smaller than those of the other compounds; however, the effect of indorenate was specific to food, whereas all the other drugs also produced significant decrements in water intake. The serotonin antagonists cinanserin, cyproheptadine, methergoline and methysergide effectively prevented the decrease in food intake produced by indorenate and fenfluramine. Haloperidol, a dopaminergic antagonist, was ineffective in preventing the effect of indorenate although it prevented the anorectic effect of amphetamine. The present results suggest the participation of serotoninergic, but not dopaminergic mechanisms, in the decrease in food intake produced by indorenate.