ANTIEMETIC EFFECTS OF A NOVEL NK-1 RECEPTOR ANTAGONIST HSP-117 IN FERRETS

We have developed a non-peptide compound, HSP-117, antagonist of the t achykinin NK-1 receptor. Binding of H-3-substance P (SP) to the membra nes of IM-9 cells was inhibited by the antagonists HSP-117 and CP-99,9 94, the inhibitory activity of HSP-117 being about 50-fold that of CP- 99,994. The SP-induced firing responses of single neuron activity in s lices of the nucleus tractus solitarius of ferrets were inhibited by 1 0 mu M HSP-117. Intracerebroventricular injection of HSP-117 significa ntly inhibited retching and vomiting induced by copper sulphate and mo rphine and the inhibitory effect of HSP-117 on emesis was greater than that of CP-99,994. These results indicate that (1) HSP-117 is a poten t anti-emetic agent, blocking NK-1 receptors in the nucleus tractus so litarius and (2) NK-1 receptors in the nucleus tractus solitarius play an important role in emesis induced by broad-spectrum emetic stimuli. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.