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Additive antiemetic efficacy of Δ 9 ‐THC with vanilloid TRPV1 receptor agonists in the least shrew (Cryptotis parva)
Author(s) -
Brar Rajivinder Singh,
Chebolu Seetha,
Zhong Weixia,
Darmani Nissar A.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1093.20
Subject(s) - resiniferatoxin , trpv1 , vomiting , antiemetic , capsazepine , pharmacology , chemistry , agonist , cisplatin , capsaicin , antagonist , anesthesia , medicine , chemotherapy , receptor , transient receptor potential channel , biochemistry
Previous studies have shown that cannabinoid CB 1 and vanilloid TRPV1 agonists ( Δ 9 ‐THC and resiniferatoxin (RTX), respectively) can attenuate the emetic effects of chemotherapeutic agents such as cisplatin. In this study we used the least shrew to demonstrate whether combination of varying doses of Δ 9 ‐THC with resiniferatoxin can produce additive antiemetic efficacy against cisplatin‐induced vomiting. RTX by itself caused vomiting in a bell‐shaped dose‐dependent manner with maximal vomiting at 18 ug/kg when administered sc but not ip. Δ 9 ‐THC up to 10 mg/kg can only protect least shrews from cisplatin‐induced emesis by 80% with an ID50 of 0.3 – 1.8 mg/kg. Combinations of 1 or 5 ug/kg RTX with varying doses of Δ 9 ‐THC completely suppressed both the frequency and the percentage of shrews vomiting with ID50 dose values 5–50 times lower than Δ 9 ‐THC doses tested alone against cisplatin. A less potent TRPV1 agonist capsaicin, by itself did not cause emesis (ip or sc), but did significantly reduce vomiting induced by cisplatin given after 30 minutes but not at 2 hours. TRPV1 antagonist ruthenium red attenuated cisplatin‐induced emesis at 5 mg/kg, however capsazepine did not. In summary, we present evidence that combinations of CB 1 and TRPV1 agonists have the capacity to completely abolish cisplatin‐induced emesis at doses lower than when used individually.