Granisetron (Hydrochloride)

Granisetron (Hydrochloride) (BRL 43694A) is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy. IC50 & Target: IC50: 17uM (5-HT3 receptor)^[1]. In Vitro: In rat forestomach GR reduced 5-HT-evoked contractions at IC50 17 /- 6 uM. In isolated rabbit heart, GR 0.003-0.03 nM dose-dependently reduced s-HT tachycardia; at high levels GR reduced submaximal and maximal responses to 5-HT^[1]. In Vivo: Leukocyte accumulation was dose-dependently inhibited by granisetron both at 6 and 72 h after induction of inflammation. Granisetron increased PGE(2) level at a lower dose (50 microg/pouch) but higher doses (100 and 200 microg/pouch) inhibited the release. At the same time, TNFalpha production was decreased by the lower dose and increased by higher doses of granisetron in a reciprocal fashion^[2]. The GTDS displayed non-inferiority to oral granisetron: complete control was achieved by 60% of patients in the GTDS group, and 65% in the oral granisetron group (treatment difference, -5%; 95% confidence interval, -13-3). Both treatments were well tolerated, the most common adverse event being constipation^[3].