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 (Zofran(TM)) 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.