Effect of a selective and potent central nervous system penetrant, neurokinin-3 receptor antagonist (SB-222200), on cisplatin-induced emesis in the ferret.

Abstract

The anti-emetic activity of selective NK-1 receptor antagonism is well established. However, little is known of the possibility that other NK receptors might also be involved in the emetic reflex. Given the reported location of NK-3 receptors within the rat brainstem vagal motor and sensory nuclei, we investigated the ability of SB-222200, a brain-penetrant NK-3 receptor antagonist, to interfere with emesis evoked in ferrets by the emetogenic cytotoxic agent cisplatin. In contrast to control anti-emetic experiments using the 5-HT3 receptor antagonist ondansetron, SB-222200 was found to have no effects on cisplatin-induced vomiting or on the associated reductions in feeding and drinking behaviors at any dose tested. We suggest that if NK-3 receptors are involved in the mechanisms of cisplatin-induced nausea and vomiting, they play only a minor role, relative to the major anti-emetic activity exhibited by 5-HT3 or NK-1 receptor antagonism.

• Authors: Andrew G King, Gareth J Sanger
• Journal: Neuroscience letters (Neurosci Lett) Vol. 376 Issue 1 Pg. 5-8 (Mar 07 2005) ISSN: 0304-3940 [Print] Ireland
• PMID: 15694264 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antiemetics
• Carrier Proteins
• Cell-Penetrating Peptides
• Quinolines
• Receptors, Neurokinin-3
• SB 222200
• Ondansetron
• penetratin
• Cisplatin

Topics

• Animals
• Antiemetics (therapeutic use)
• Behavior, Animal (drug effects)
• Carrier Proteins (therapeutic use)
• Cell-Penetrating Peptides
• Cisplatin
• Dose-Response Relationship, Drug
• Drug Interactions
• Ferrets
• Male
• Ondansetron (therapeutic use)
• Quinolines (therapeutic use)
• Reaction Time (drug effects)
• Receptors, Neurokinin-3 (antagonists & inhibitors)
• Time Factors
• Vomiting (chemically induced, drug therapy)