Vomiting may be induced by a variety of agents such as drugs, oncolytics, and provocative motion, as well as being conditioned to occur to environmental stimuli. Such
emesis has recently been shown to be blocked by agonists at the 5-HT1A subtype of
serotonin receptor. The
antiemetic effects of
LY228729 [(-)-4-(dipropylamine)-1,3,4,5-tetrahydrobenz-(c,d)
indole-6- carboxamide], a
5-HT1A receptor agonist, were tested and compared to the
antiemetic effects of the
5-HT3 receptor antagonists
ondansetron,
tropisetron, and
MDL 72222 (3-tropanyl-3,5-dichlorobenzoate). The
emetic stimuli tested are known to be blocked by
5-HT3 antagonists in species other than the pigeon. In the pigeon,
LY228729 totally abolished
vomiting induced by fully
emetic doses of
cisplatin (10 mg/kg),
ipecac (3 ml/kg),
emetine (10 mg/kg), and a
5-HT3 agonist, m-(chlorophenyl)-
biguanide (1.25 mg/kg).
MDL 72222 blocked
ipecac-induced
vomiting in a dose-related manner and was partially effective in attenuating
cisplatin-induced
emesis.
Ondansetron and
tropisetron were partially effective in blocking
emetine- and
mCPBG-induced
vomiting.
Ondansetron exhibited an intrinsic
emetic response that could not be blocked by MDL 7222, but which was eliminated by
LY228729. It was concluded that 5-HT1A agonists are more effective in the pigeon than are
5-HT3 antagonists against these types of
emetic stimuli. These results broaden the range of
emetic stimuli that are blocked by 5-HT1A agonists in the pigeon.