Comparison of the neurokinin-1 antagonist GR205171, alone and in combination with the 5-HT3 antagonist ondansetron, hyoscine and placebo in the prevention of motion-induced nausea in man.

Abstract

AIMS:

In man a neurokinin-1 (NK1) receptor antagonist has previously been shown to be ineffective in the prevention of motion-induced nausea. The antiemetic efficacy of NK1 receptor antagonists against chemotherapy-induced emesis is, however, enhanced when combined with a 5-HT3 receptor antagonist. Hence the efficacy of the NK1 antagonist GR205171 in combination with the 5-HT3 antagonist ondansetron (Zofrantrade mark) was assessed in motion-induced nausea.

METHODS:

GR205171 25 mg i.v., with and without concomitant administration of ondansetron 8 mg i.v., and hyoscine hydrobromide 0. 6 mg orally (positive control) were compared with placebo in a model of motion-induced nausea. The study was performed to a four-period, randomized, balanced, double-blind, crossover design in 16 healthy subjects. The end-point was the exposure to the motion stimulus required to produce moderate nausea in the subjects.

RESULTS:

The motion stimulus required to produce moderate nausea was significantly greater for the positive control than placebo (P < 0. 001). There was no significant difference between either GR205171 or GR205171 plus ondansetron and placebo (P = 0.648 and 0.342, respectively).

CONCLUSIONS:

The enhancement of NK1 receptor antagonist antiemetic activity through combination with a 5-HT3 receptor antagonist is not replicated in motion-induced nausea.

• Authors: K Reid, J L Palmer, R J Wright, S A Clemes, C Troakes, H S Somal, F House, J R Stott
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 50 Issue 1 Pg. 61-4 (Jul 2000) ISSN: 0306-5251 [Print] England
• PMID: 10886120 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Antiemetics
• Neurokinin-1 Receptor Antagonists
• Piperidines
• Serotonin Antagonists
• Tetrazoles
• Ondansetron
• Scopolamine
• vofopitant

Topics

• Adolescent
• Adult
• Antiemetics (therapeutic use)
• Cross-Over Studies
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Male
• Middle Aged
• Motion Sickness (prevention & control)
• Nausea (prevention & control)
• Neurokinin-1 Receptor Antagonists
• Ondansetron (therapeutic use)
• Piperidines (therapeutic use)
• Scopolamine (therapeutic use)
• Serotonin Antagonists (therapeutic use)
• Tetrazoles (therapeutic use)