title: Anti-emetic effects of a novel NK-1 receptor antagonist HSP-117 in ferrets.
abstract: We have developed a non-peptide compound, HSP-117, antagonist of the tachykinin NK-1 receptor. Binding of 3H-substance P (SP) to the membranes of IM-9 cells was inhibited by the antagonists HSP-117 and CP-99,994, 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 slices of the nucleus tractus solitarius of ferrets were inhibited by 10 microM HSP-117. Intracerebroventricular injection of HSP-117 significantly inhibited retching and vomiting induced by copper sulphate and morphine 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 potent anti-emetic agent, blocking NK-1 receptors in the nucleus tractus solitarius and (2) NK-1 receptors in the nucleus tractus solitarius play an important role in emesis induced by broad-spectrum emetic stimuli.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan. rsaito@psat.fukuoka-u.ac.jp
authors.forename: R
authors.initials: R
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Suehiro
authors.forename: H
authors.initials: H
authors.lastname: Ariumi
authors.forename: K
authors.initials: K
authors.lastname: Migita
authors.forename: N
authors.initials: N
authors.lastname: Hori
authors.forename: T
authors.initials: T
authors.lastname: Hashiguchi
authors.forename: M
authors.initials: M
authors.lastname: Sakai
authors.forename: M
authors.initials: M
authors.lastname: Saeki
authors.forename: Y
authors.initials: Y
authors.lastname: Takano
authors.forename: H
authors.initials: H
authors.lastname: Kamiya
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000494:pharmacology*; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology*; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D019327:Copper Sulfate; D004639:Emetics; D005289:Ferrets; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology; D014839:Vomiting / Q000517:prevention & control
chemical_list: D000932:Antiemetics; D001572:Benzofurans; D004639:Emetics; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; D009020:Morphine; C119466:HSP 117; D019327:Copper Sulfate