Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat.
5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.
Lucot
J B
JB
Wright State University, Department of Pharmacology, Dayton, OH 45435.
D000818:Animals; D000932:Antiemetics / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use; D001643:Bridged Bicyclo Compounds / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002415:Cats; D002945:Cisplatin / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D007211:Indoles / Q000627:therapeutic use; D009041:Motion Sickness / Q000188:drug therapy*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000627:therapeutic use; D013843:Thiazines / Q000037:antagonists & inhibitors*; D014326:Tropanes / Q000627:therapeutic use; D000077526:Tropisetron; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*; D014991:Xylazine / Q000009:adverse effects / Q000037:antagonists & inhibitors*
D000932:Antiemetics; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013843:Thiazines; D014326:Tropanes; D014991:Xylazine; D000077526:Tropisetron; C055971:zacopride; C042253:bemesetron; D002945:Cisplatin