(±)-Ibipinabant ((±)-SLV319) has been utilized in clinical trials for the treatment of obesity and type 2 diabetes.

CB1
:22nM

Cannabinoid receptor 1 (CB1R) antagonists are promising for obesity treatment, but adverse effects limit clinical use. Ibipinabant is a potent [Ki (CB1) = 7.8 nM] and selective [Ki (CB2) = 7.943 nM] CB1 antagonist, demonstrating in vitro properties similar to rimonabant, including inverse agonism, brain penetration[3], and high affinity [pA2 for arachidonic acid release in CHO cells = 9.9].

Ibipinabant (3 mg/kg) significantly lowers unfasted glucose levels compared to rimonabant at equivalent doses on days 17, 28, and 38. Long-term ibipinabant administration notably slows diabetes progression in ZDF rats by moderating the rise in blood glucose and HbA1c levels over time. Additionally, ibipinabant decreases the evident hyperinsulinemia at 6-8 weeks of age and mitigates the sharp decline in insulin levels occurring 1-2 weeks thereafter[3].

Rats: SLV319, rimonabant and rosiglitazone are suspended in a 10% dimethylacetamide, 10% cremophor, 10% ethanol and 70% water vehicle. Drugs are administered by oral gavage in a volume of 2 mL/kg body weight at 09:00 hours every day. Treatment groups are as follows: (i) Vehicle: ad libitum access to food (vehicle), (ii) Vehicle: restricted access to food (20% less than average food intake of ad libitum vehicle-treated group for the first 3 days of the study, then 10% less than the average food intake of the ad libitum vehicle-treated group for the remainder of the study) (restricted), (iii) Rosiglitazone (4 mg/kg), (iv) Rimonabant (3 mg/kg) (RIM 3 mg/kg), (v) Rimonabant (10 mg/kg) (RIM 10 mg/kg), (vi) SLV319 (3 mg/kg) (IBI 3 mg/kg) and (vii) Ibipinabant (10 mg/kg) (IBI 10 mg/kg). Rosiglitazone is used as a positive control for its ability to delay β-cell decline, and rimonabant is used as a positive control for CB1 antagonism[3].