Ibipinabant (SLV319) is a potent, selective, and orally active antagonist of the cannabinoid CB1 receptor, demonstrating a K i of 7.8 nM and exhibiting over 1000-fold selectivity for CB1 compared to CB2 (K i =7943 nM). It is utilized in obesity and diabetes research [1] [2] [3].

SLV319 displaces the specific CP-55940 (CB agonist) binding in CHO cells stably transfected with human CB1 receptor, with a K i of 7.8 nM [1]. WIN-55212 (CB1 agonist)-induced arachidonic acid release in CHO cells is antagonized by SLV319 concentration-dependently with a pA2 of 9.9 [1].

SLV319 (3 mg/kg/day; p.o. for 28 d) reduces the food intake, body weight, and hormonal/metabolic abnormalities in diet-induced obesity (DIO) mice [2]. SLV319 (3 mg/kg/day, p.o. for 28 d) reverses the HFD-induced increase in adipose tissue leptin mRNA [2]. SLV319 (3-10 mg/kg; daily oral gavage for 56 d) shows weight loss-independent antidiabetic effects and attenuates β-cell loss in a rat model of progressive β-cell dysfunction [3]. SLV319 (oral administration) antagonizes CB agonist (CP55940) induced hypotension in rats and hypothermia in mice, with an ED 50 of 5.5 and 3 mg/kg, respectively [1]. Animal Model: Six-week-old male C57Bl/6J mice received a diet containing 60% of calories as fat, resulting in body weights >42 g in 12-14 weeks [2] Dosage: 3 mg/kg/day Administration: P.o. for 28 days Result: Caused reductions in food intake, body weight and adiposity in DIO mice.