European Journal of Pharmacology, 145 (1988) 227-230 227 Elsevier EJP 20051 Short communication Ketanserin antagonises the anorectic effect of DL-fenfluramine in the rat Graeme Hewson *, Glynis E. Leighton, Raymond G. Hill and John Hughes Parke-Davis Research Unit, Addenbrookes Hospital Site, Hills Road, Cambridge CB2 2QB, U.K. Received 9 November 1987, accepted 10 November 1987 To determine the role played by 5-HT 2 receptors in the anorectic action of DL-fenfluramine, the ability of the selective 5-HT2 receptor antagonist ketanserin to block the reduction in food intake produced by this drug was investigated in non-deprived rats. Ketanserin (1 and 2.5 mg/kg i.p.) produced a dose-dependent antagonism of the anorectic effect of DL-fenfluramine (3 mg/kg i.p.). Prazosin (1 mg/kg i.p.) did not antagonise this effect. It is concluded that the anorectic actions of DL-fenfluramine are mediated via 5-HT2 receptors. Ketanserin; Prazosin; DL-Fenfluramine anorexia 1. Introduction DL-Fenfluramine is an anorectic agent used clinically in the treatment of obesity. Although its precise mechanism of action remains unclear, it is generally accepted that fenfluramine exerts its anorectic activity by selectively enhancing sero- toninergic mechanisms in the brain (Garattini et al., 1986). In support of such a mechanism, antagonists at 5-hydroxytryptamine (5-HT) recep- tors, such as methysergide and metergoline, have been shown to attenuate the reductions in food intake produced by fenfluramine (Barrett and Mc- Sharry, 1975; Carruba et al., 1986). Recently, three subtypes of 5-HT receptor have been defined, based on the use of selective antagonists (Bradley et al., 1986). The present study investigated the effect of the selective 5-HT 2 receptor antagonist ketanserin (Leysen et al., 1981) on the reduction in food intake produced by DL- fenfluramine. As ketanserin can also block al- adrenoceptors (Fozard, 1982), the effects of the * To whom all correspondence should be addressed. selective cq-adrenoceptor antagonist prazosin on the anorectic action of DL-fenfluramine was also determined. 2. Materials and methods 2.1. Animals Male Hooded Lister rats (Olac, starting weight 175-200 g) were used. They were housed individu- ally at a constant room temperature (21 ° C) and maintained on a 12 h light : 12 h dark cycle (lights on 07:00 h). 2.2 Drugs Ketanserin tartrate (Janssen) and DL-fen- fluramine hydrochloride (Sigma) were dissolved in distilled water. Prazosin hydrochloride (Pfizer) was dissolved in 0.01 N tartaric acid (final pH of solution 4-5). All drugs were injected i.p. in a volume of 1 ml/kg. Doses refer to the weight of free base. 0014-2999/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)