Norbuprenorphine is a major active metabolite of the opioid modulator buprenorphine. It is a μ-opioid, δ-opioid, and nociceptin receptor full agonist, and a κ-opioid receptor partial agonist. In rats, unlike buprenorphine, norbuprenorphine produces marked respiratory depression but with very little antinociceptive effect. In explanation of these properties, norbuprenorphine has been found to be a high affinity P-glycoprotein substrate, and in accordance, shows very limited blood-brain-barrier penetration.