Methocinnamox (M-CAM) is a selective μ-opioid receptor (MOR) antagonist with a Ki of 0.6 nM, known for its long-lasting receptor binding. Its extended activity results from non-covalent attachment to the MOR orthosteric site, which leads to prolonged receptor blockade requiring new receptor synthesis for function restoration. Additionally, Methocinnamox reversibly antagonizes κ-opioid receptors (KOR) (Ki = 4.9 nM) and δ-opioid receptors (DOR) (Ki = 2.2 nM) without exhibiting intrinsic agonistic activity. This compound can be utilized for reversing and preventing opioid overdose and use disorders.

μ Opioid Receptor/MOR:0.6 nM (Ki)

Methocinnamox binds tightly to μ receptors in mouse brain tissue, exhibiting a very slow dissociation rate, while having no effect on the binding sites for δ and κ receptors. Additionally, Methocinnamox irreversibly blocks the ability of DAMGO, psychoactive compounds, and morphine to inhibit cAMP accumulation in HEK293 cells transfected with human μ opioid receptors.

A single subcutaneous dose of Methocinnamox (10 mg/kg) effectively counteracts various morphine-induced effects in rats, such as analgesia, respiratory depression, gastrointestinal inhibition, and temperature changes, with the antagonistic effects lasting over two weeks. Additionally, Methocinnamox (0.0001-10 mg/kg administered intravenously or 10 mg/kg both intravenously and subcutaneously, single dose) can reverse and protect against respiratory depression caused by psychoactive compounds in rats. In rhesus monkeys, Methocinnamox (0.32 mg/kg, subcutaneous, administered once or every 12 days for a total of 5 doses; 0.032 mg/kg, daily for 21 days) reduces opioid self-administration behavior.