Peripheral and central NK1 receptors in emesis control in Suncus murinus

Brain penetrant tachykinin NK 1 receptor antagonists are known to reduce cisplatin‐induced emesis in ferrets. In the present studies, we investigate the role of central versus peripheral NK 1 receptors in the mechanism of emesis in S. murinus . R116301 was selected as a reference brain penetrant NK 1 receptor antagonist, and R115614 was used as a peripherally restricted antagonist; both have similar affinity for S. murinus NK 1 receptors (PA 2 ~8) and in vivo potency to reduce substance P‐induced plasma extravasation (ID 50 ~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.5H 2 O (480.6 μmol/kg, i.g.), or cisplatin (100 μmol/kg, i.p). Peripheral Studies R116301 (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 Studies R116301 (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 NK 1 receptors play an important role in the emetic reflex but peripherally located NK 1 receptors may also be involved in some causes of emesis.