samidorphan

Samidorphan is a novel small molecule opioid receptor modulator developed primarily as an adjunct to antipsychotic therapy. It is structurally related to naltrexone and acts as an antagonist at the μ-opioid receptor (MOR) when signaling through Gαi proteins, a partial agonist at MOR via other G-proteins, and a partial agonist at both κ- and δ-opioid receptors. Samidorphan has high affinity for μ-, κ-, and δ-opioid receptors, with its primary in vivo action being μ-opioid antagonism. Its main clinical use is in combination with olanzapine (as the fixed-dose product Lybalvi) for treating schizophrenia and bipolar I disorder, where it helps mitigate olanzapine-induced weight gain by modulating opioid signaling involved in feeding and metabolism. As a standalone drug or in other combinations (e.g., with buprenorphine), development has been discontinued or not pursued further[1][5].

Brand names

Lybalvi

Other names

3-carboxamido-4-hydroxynaltrexone