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Comparison of the neurokinin‐1 antagonist GR205171, alone and in combination with the 5‐HT 3 antagonist ondansetron, hyoscine and placebo in the prevention of motion‐induced nausea in man
Author(s) -
Reid K.,
Palmer J. L.,
Wright R. J.,
Clemes S. A.,
Troakes C.,
Somal H. S.,
House F.,
Stott J. R. R.
Publication year - 2000
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2000.00221.x
Subject(s) - ondansetron , antiemetic , nausea , antagonist , placebo , motion sickness , crossover study , receptor antagonist , pharmacology , anesthesia , medicine , receptor , radiology , alternative medicine , pathology
AimsIn man a neurokinin‐1 (NK 1 ) receptor antagonist has previously been shown to be ineffective in the prevention of motion‐induced nausea. The antiemetic efficacy of NK 1 receptor antagonists against chemotherapy‐induced emesis is, however, enhanced when combined with a 5‐HT 3 receptor antagonist. Hence the efficacy of the NK 1 antagonist GR205171 in combination with the 5‐HT 3 antagonist ondansetron (Zofran ™ ) was assessed in motion‐induced nausea.MethodsGR205171 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.ResultsThe 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).ConclusionsThe enhancement of NK 1 receptor antagonist antiemetic activity through combination with a 5‐HT 3 receptor antagonist is not replicated in motion‐induced nausea.