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

CB1:7.8 nM (Ki), CB2:7943 nM (Ki)

SLV319 competitively inhibits CP-55940 (CB agonist) binding to the human CB1 receptor in CHO cells genetically modified to express this receptor, exhibiting an inhibition constant (K i) of 7.8 nM [1]. Furthermore, SLV319 dose-dependently antagonizes the WIN-55212 (CB1 agonist)-induced release of arachidonic acid in these cells, demonstrating a potency (pA2) of 9.9 [1].

SLV319, administered orally at a dosage of 3 mg/kg/day for 28 days, effectively reduces food intake, body weight, and hormonal/metabolic abnormalities in diet-induced obesity (DIO) mice, as well as reverses high-fat diet (HFD)-induced increases in adipose tissue leptin mRNA. At doses ranging from 3-10 mg/kg given daily via oral gavage for 56 days, SLV319 also demonstrates weight loss-independent antidiabetic effects and mitigates β-cell loss in a rat model of progressive β-cell dysfunction. Furthermore, SLV319 counters CB agonist (CP55940)-induced hypotension in rats and hypothermia in mice, showcasing ED 50 values of 5.5 and 3 mg/kg, respectively. In an animal model involving six-week-old male C57Bl/6J mice fed a diet of 60% calories from fat, resulting in body weights exceeding 42 g within 12-14 weeks, a similar dosage and administration method led to significant reductions in food intake, body weight, and adiposity in DIO mice.