The antiemetic interaction of Delta9-tetrahydrocannabinol when combined with tropisetron or dexamethasone in the least shrew.
5-HT3 receptor antagonists (e.g. tropisetron) combined with dexamethasone are effective for the acute phase of cisplatin (CIS)-induced emesis. This study determined the possible additive or synergistic antiemetic efficacy of Delta9-THC when combined with tropisetron or dexamethasone (DEX). Delta9-THC (0-10 mg/kg i.p.) was injected in combination with tropisetron (0-5 mg/kg i.p.) or dexamethasone (0-20 mg/kg i.p.) prior to CIS (20 mg/kg i.p.) in the least shrew, and the induced emesis was recorded for 60 min. CIS-induced vomiting was dose-dependently and significantly attenuated by individual administration of Delta9-THC (59-97% reductions) and tropisetron (79-100% attenuation), but not dexamethasone (26-40%), although a trend (p<0.1) towards reduced vomiting frequency following DEX was noted. Low doses of Delta9-THC (0.25 or 0.5 mg/kg) when combined with low doses of tropisetron (0.025, 0.1, or 0.25 mg/kg) were more efficacious in reducing emesis frequency than when given individually, but Delta9-THC had no antiemetic interactions with DEX. However, no tested combination provided a significantly greater effect on the number of animals vomiting than their individually-administered counterparts. The modest interaction of Delta9-THC with tropisetron suggests they activate overlapping antiemetic mechanisms, while the lack of interaction with dexamethasone needs further clarification.
Wang
Yaozhi
Y
Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854, United States.
Ray
Andrew P
AP
McClanahan
Bryan A
BA
Darmani
Nissar A
NA
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D000970:Antineoplastic Agents; D002945:Cisplatin; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D012788:Shrews / Q000502:physiology*; D000077526:Tropisetron; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
D000932:Antiemetics; D000970:Antineoplastic Agents; D007211:Indoles; D000077526:Tropisetron; D013759:Dronabinol; D003907:Dexamethasone; D002945:Cisplatin