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Neuropharmacology

The differential antiemetic properties of GLP-1 receptor antagonist, exendin (9-39) in Suncus murinus (house musk shrew).


PMID 24726308

Abstract

The use of glucagon-like peptide-1 (7-36) amide (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus is commonly associated with nausea and vomiting. Previous studies using Suncus murinus revealed that the GLP-1 receptor agonist, exendin-4, induces emesis via the brainstem and/or hypothalamus. The present study investigated the mechanism of exendin-4-induced emesis in more detail. Ondansetron (1xa0mg/kg, s.c.) and CP-99,994 (10xa0mg/kg, s.c) failed to reduce emesis induced by exendin-4 (3xa0nmol, i.c.v.), suggesting that 5-HT3 and NK1 receptors are not involved in the mechanism. In other studies, the GLP-1 receptor antagonist, exendin (9-39), antagonised emesis and c-Fos expression in the brainstem and the paraventricular hypothalamus induced by the chemotherapeutic drug cisplatin (30xa0mg/kg, i.p.; pxa0xa00.05), or copper sulphate pentahydrate (120xa0mg/kg, p.o.; pxa0>xa00.05). GLP-1 receptors may therefore represent a potential target for drugs to prevent chemotherapy-induced emesis in situations where 5-HT3 and NK1 receptor antagonists fail.