The efficacy of various classes of anti-emetics in preventing deoxynivalenol-induced vomiting in swine.

The Fusarium mycotoxin deoxynivalenol (DON) is a potent emetic agent. While the basic mechanisms which invoke and mediate emesis are still poorly understood, various neurotransmitters appear to be involved. The action of these transmitters can be blocked by various receptor-specific antagonists. The current study investigated the efficacy of several classes of receptor antagonists to block the emetic effect of DON. Following anti-emetic pretreatment, pigs were administered the toxin (i.v., 80 micrograms/kg, or oral, 300 micrograms/kg) and the onset of emesis was monitored. Certain specific serotonin (5HT3)-receptor antagonists (ICS 205-930, BRL 43694 A) were found to efficaciously prevent DON-induced vomiting. These observations support the hypothesis that serotonin plays an important role in chemically induced emesis. Also moderately effective, but requiring high doses, were the 5HT2-receptor antagonists, cyproheptadine and sulpiride. A variety of compounds possessing strong anticholinergic activity were also efficacious. These, however, apparently act directly at the emetic center and thus are capable of preventing emesis regardless of the cause, including chemically induced vomiting. Non-effective were the antihistaminic and antidopaminergic anti-emetics; except, those which also possessed considerable anticholinergic activity, and i.v. administered chlorpromazine which has been speculated to block specific receptors found in the brain's chemoreceptor trigger zone (CTZ) reportedly involved in initiating emesis.