Peripheral and central NK1 receptors in emesis control in Suncus murinus

Abstract

Brain penetrant tachykinin NK1 receptor antagonists are known to reduce cisplatin‐induced emesis in ferrets. In the present studies, we investigate the role of central versus peripheral NK1 receptors in the mechanism of emesis in S. murinus. R116301 was selected as a reference brain penetrant NK1 receptor antagonist, and R115614 was used as a peripherally restricted antagonist; both have similar affinity for S. murinus NK1 receptors (PA2~8) and in vivo potency to reduce substance P‐induced plasma extravasation (ID50 ~2.9 μmol/kg). Drugs or vehicle were administered s.c, or i.c.v. 30 min prior to nicotine (30.7 μmol/kg, s.c.), copper sulphate.5H2O (480.6 μmol/kg, i.g.), or cisplatin (100 μmol/kg, i.p).Peripheral StudiesR116301 (23–53 mmol/kg, s.c) attenuated nicotine‐ and cisplatin‐induced emesis by 76 and 52 %, respectively (P<0.05). R115614 (30–70 mmol/kg, s.c) reduced copper sulphate‐ and cisplatin‐induced emesis by 75 and 50 %, respectively (P<0.05).Central StudiesR116301 (10–100 nmol, i.c.v.) antagonised nicotine‐induced emesis 89 % (P<0.05), while R115614 (100–500 nmol, i.c.v.) was incative (P>;0.05). In conclusion, centrally located tachykinin NK1 receptors play an important role in the emetic reflex but peripherally located NK1 receptors may also be involved in some causes of emesis.