norbuprenorphine

Norbuprenorphine is a major active metabolite of buprenorphine, formed via N-dealkylation primarily by CYP3A4. It is a potent agonist at the μ-opioid (mu), δ-opioid (delta), and nociceptin receptors, and acts as a partial agonist at the κ-opioid (kappa) receptor. Norbuprenorphine exhibits high affinity for these opioid receptors, with full agonist activity at μ-, δ-, and nociceptin receptors, but only partial agonism at κ-receptors[1][4][5]. Unlike its parent compound buprenorphine—which is used clinically for pain management and opioid dependence—norbuprenorphine itself has minimal antinociceptive effects but produces marked respiratory depression in animal models[1][5]. This difference in pharmacological profile may be due to its limited penetration across the blood-brain barrier as it is a high-affinity substrate for P-glycoprotein efflux transporters[1][5]. Norbuprenorphine also acts as an aryl hydrocarbon receptor (AhR) agonist, inducing expression of breast cancer resistance protein (BCRP/ABCG2) in human placental cells[3]. It is not marketed as a drug on its own but can be detected in patients treated with buprenorphine.

Other names

NBUP