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The broad‐spectrum anti‐emetic activity of the novel non‐peptide tachykinin NK 1 receptor antagonist GR203040
Author(s) -
Gardner C.J.,
Twissell D.J.,
Dale T.J.,
Gale J.D.,
Jordan C.C.,
Kilpatrick G.J.,
Bountra C.,
Ward P.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15118.x
Subject(s) - suncus , pharmacology , antagonist , nk1 receptor antagonist , receptor antagonist , cisplatin , antiemetic , chemistry , receptor , substance p , neuropeptide , vomiting , biology , medicine , endocrinology , chemotherapy
1 Following our earlier observations that the tachykinin NK 1 receptor antagonist CP‐99,994 is an effective anti‐emetic in ferrets, we have examined the anti‐emetic effects of a more potent and novel NK 1 receptor antagonist, GR203040, against various emetic stimuli in the ferret, dog and house musk shrew (Suncus murinus) . 2 In ferrets, GR203040 (0.1 mg kg −1 s.c. or i.v.) is effective against emesis induced by radiation, cisplatin, cyclophosphamide, copper sulphate, ipecacuanha or morphine. 3 In animals in which emesis had been established with cisplatin, GR203040 (1 mg kg −1 s.c.) was fully effective as an interventional treatment. No further emesis was seen in animals treated with GR203040 whilst saline‐treated animals continued to vomit. 4 GR203040 (0.1 mg kg −1 s.c.) retains anti‐emetic efficacy in the ferret, even when given as a 6 h pretreatment, indicating that this compound has a long duration of action. The compound is also effective orally at the same dose, when given as a 90 min pretreatment. 5 GR203040 (0.1 mg kg −1 i.v.) is fully effective against ipecacuanha‐induced emesis in the dog. 6 GR203040 is effective against motion‐and cisplatin‐induced emesis in Suncus murinus . These effects were seen at doses an order of magnitude greater than those shown to be effective against cisplatin in the ferret. 7 In conclusion, GR203040 is a novel anti‐emetic agent, and the broad spectrum of anti‐emetic activity, together with activity observed in three species, suggests that this compound is worthy of clinical investigation.