Potent inhibition of both the acute and delayed emetic responses to cisplatin in piglets treated with GR205171, a novel highly selective tachykinin NK₁ receptor antagonist

Abstract

1 The eects of GR205171, a selective tachykinin NK 1 receptor antagonist, were investigated on both the acute and delayed phases of cisplatin-induced nausea-like behaviour and vomiting in the conscious piglet. ) every 6 h throughout the experiment. 3 The latencies of the ®rst emetic episode (EE) and nausea-like behavioural episode (NE) increased in all experimental groups treated at T0 715 min , and the total number of both EE and NE during the 60 h was reduced in a dose-dependent manner. In piglets treated at T0 715 min with GR205171 1 mg kg 71 , eight out of 13 (62%) did not vomit throughout the experiment. Animals treated with GR205171 (1 mg kg 71) at T16 715 min exhibited an acute response to cisplatin but did not vomit during the delayed phase. The greatest inhibition of both nausea-like behaviour and vomiting was observed in piglets receiving multiple injections of GR205171. 4 These results demonstrate the long-lasting anti-emetic eects of GR205171, and con®rm the key role of substance P within the emetic re¯ex.

Aprepitant: A substance P antagonist for chemotherapy induced nausea and vomiting

“…[24] The protection in delayed emesis was superior in comparison with A study by de Wit et al [29] granisetron. So a broader spectrum of activity with a of antiemetic effect of aprepitant in patients receiving variety of emetic stimuli and prominent activity in multiple cycles of cisplatin-based chemotherapy.…”

Treatment of nausea and vomiting in advanced cancer

“…NK 1 receptor antagonists inhibit substance P release in the area of the nucleus ambiguus [82,83]. Although the inhibition of substance P has been disputed [84].…”

Novel Approaches to the Treatment of Nausea and Vomiting

“…shown to prevent acute and delayed vomiting after cisplatinum administration [46,47]. More recently in an investigation of patients receiving cisplatinum, the NK-1 receptor antagonist L-754,030 given in addition to emesis, they incompletely relieve the associated nausea which may impair daily functioning to a greater degree standard prophylaxis with granisetron and dexamethasone produced substantial reductions in acute vomiting than the vomiting [1].…”