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: R Saito, Y Suehiro, H Ariumi, K Migita, N Hori, T Hashiguchi, M Sakai, M Saeki, Y Takano, H Kamiya
• Journal: Neuroscience letters (Neurosci Lett) Vol. 254 Issue 3 Pg. 169-72 (Oct 02 1998) ISSN: 0304-3940 [Print] Ireland
• PMID: 10214984 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antiemetics
• Benzofurans
• Emetics
• Neurokinin-1 Receptor Antagonists
• Piperidines
• 3-(2-methoxybenzylamino)-2-phenylpiperidine
• Substance P
• Morphine
• HSP 117
• Copper Sulfate

Topics

• Animals
• Antiemetics (administration & dosage, pharmacology)
• Benzofurans (administration & dosage, pharmacology)
• Brain Stem (drug effects, physiology)
• Cerebral Ventricles (drug effects, physiology)
• Copper Sulfate
• Emetics
• Ferrets
• In Vitro Techniques
• Injections, Intraventricular
• Male
• Membrane Potentials (drug effects)
• Morphine (pharmacology)
• Neurokinin-1 Receptor Antagonists
• Piperidines (administration & dosage, pharmacology)
• Substance P (metabolism, pharmacology)
• Vomiting (prevention & control)