Sigma receptor-mediated emetic response in pigeons: agonists, antagonists and modifiers.

In order to more fully characterize sigma ligand-induced emesis in the pigeon, the effects of a number of compounds were tested alone or in combination with ditolyguanidine (DTG). The drugs tested could be categorized into three types: agonists, which produced the emetic response (DTG > amitriptyline > BD 737 > thioridazine), antagonists, which effectively antagonized the effects of DTG (haloperidol > BMY 14802 > BD 1139 > chlorpromazine), and agents which did not produce the emetic response on their own, but potently enhanced the emetic effect of DTG (BD-1008 > or = phencyclidine > (+)-n-allylnormetazocine > or = propranolol). Chronic haloperidol resulted in a markedly diminished emetic response to DTG, which returned to control levels by 24.5 days. Haloperidol, but not BMY 14802, was effective in antagonizing the lethal effects of DTG. These data suggest further in vivo evidence for a functional mediation by sigma sites of the emetic response to DTG in the pigeon, and may provide in vivo evidence for potential allosteric modification of sigma ligands.