The α1-adrenoceptor antagonist/5-hydroxy-tryptamine1A agonist urapidil improves glucose disposition in streptozotocin diabetic rats

Abstract

O-31 Introduction: Urapidil (U) is an established drug in the treatment of hypertension. Serotonin1A-(5-HT1A) agonists impair glucose metabolism [1]. We investigated, possible adverse metabolic effects of U due to its 5-HT1A agonistic properties in streptozotocin diabetic rats. Methods: Male Wistar Kyoto Rats were made diabetic by streptozotocin i.p. and randomized (n = 6) to four treatment groups (U3: U 3 mg kg−1 (2×/day) PO, U10: U 10 mg kg−1 2×/day PO, U30: U30 mg kg−1 2×/day PO, insulin 2 IU kg−1 2×/day s.c.). Results: 7 days' treatment with U 10 mg kg−1 and U 30 mg kg−1 2×/day decreased mean blood glucose values significantly (U10: 281 ± 20 mg dL−1, P = 0.024; U30: 285 ± 15 mg dL−1, P = 0.04) in comparison to diabetic control (376 ± 15 mg dL−1). Insulin treatment normalized blood glucose levels (Fig. 1).FigureConclusion: Urapidil, even in high doses, has no disadvantage on circulating glucose concentration in experimental diabetes mellitus despite its 5-HT1A agonistic properties. Possibly the α1-antagonistic properties counteract the 5-HT1A receptor-mediated negative metabolic effects [2].