Antiemetic effects of 5-HT1A agonists in the pigeon.
Ditolyguanidine (DTG) induced a dose-dependent emetic response in pigeons, with 100% of the birds vomiting after 5.6 mg/kg. Retching and vomiting originally induced by DTG could be conditioned to the test situation. Both the unconditioned and conditioned emetic responses were dose-dependently blocked by 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT) and LY228729, agonists at the 5-HT1A subtype of serotonin receptor, but not by the 5-HT3, antagonist tropisetron. Higher doses (0.25-0.5 mg/kg) of tropisetron exhibited intrinsic emetic activity which could also be prevented by 8-OH-DPAT. NAN-190, a putative 5-HT1A partial agonist, produced both an antiemetic response when administered before DTG and also attenuated the antiemetic effects of 8-OH-DPAT. Pentobarbital blocked the conditioned, but not the unconditioned DTG-induced emesis. These results support the possibility that 5-HT1A agonists exhibit antiemetic activity against a broad range of emetic stimuli, including conditioned vomiting which is usually resistant to pharmacological attenuation.
Wolff
M C
MC
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
Leander
J D
JD
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000932:Antiemetics / Q000494:pharmacology*; D010856:Columbidae; D003214:Conditioning, Classical / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004639:Emetics / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000927:Anticonvulsants; D000932:Antiemetics; D018491:Dopamine Agonists; D004639:Emetics; D006146:Guanidines; D010880:Piperidines; D017366:Serotonin Receptor Agonists; C026539:preclamol; D010424:Pentobarbital; C050232:1,3-ditolylguanidine