The site of the anti-emetic action of tachykinin NK1 receptor antagonists may exist in the medullary area adjacent to the semicompact part of the nucleus ambiguus

NK1 receptor antagonists have been shown to act centrally and to produce a broad-spectrum anti-emetic action. To determine precisely the site of this action, we microinjected GR205171, an NK1 receptor antagonist, into the lef t medulla oblongata in decerebrate paralyzed dogs. The right medulla was tr ansected 2.5 mm rostral to the obex to eliminate the emetic function of tha t half. Fictive retching induced by vagal stimulation was still observed af ter each of 32 injections (0.5-5 mu g in 1-30 mu l) in the area ventrolater al to the solitary complex in six dogs. Retching was also observed for 30 m in or more after all but 2 of 30 injections (0.5-1 mu g in 0.5-1 mu l) in t he area dorsal to the retrofacial nucleus in 17 dogs. In contrast, retching disappeared within 5-30 min after each of 20 injections (0.5-1 mu g in 1 m u l) in the area adjacent to the semicompact part of the nucleus ambiguus ( scAMB) in 15 dogs. The threshold dose for abolition of the retching respons e was examined in seven dogs and was about 0.1 ng in 1 mu l. The maximum ve locity of salivation occurred before the onset of retching and significantl y decreased after its abolition. These results suggest that the site of the anti-emetic action of NK1 receptor antagonists may lie in a limited area a djacent to the scAMB, and that neurons in the site induce prodromal signs a nd retching in a sequential manner. (C) 1999 Elsevier Science B.V. All righ ts reserved.