Org 27569

Org 27569 is a potent CB1 receptor allosteric modulator (pEC50 = 8.24). Org 27569 inhibits CB1 receptor antagonist efficacy in vitro (pKb = 7.57). Org 27569 binds to a regulatory site on the CB1 receptor target, causing a conformational change that increases the binding affinity of CB1 agonists such as CP 55,940, while decreasing the binding affinity of CB1 antagonists or inverse agonists such as rimonabant. Org 27569 significantly increases binding of the CB1 agonist [3H]CP 55.940 (pKb = 5.67) and decreases binding of the CB1 inverse agonist [3H]SR 141716A (pKb = 5.95), and so in practice behaves as an insurmountable antagonist of CB1 receptor function.