Norbuprenorphine

Norbuprenorphine.svg

Norbuprenorphine is an active metabolite of the opioid buprenorphine. It is formed in the liver through the N-dealkylation of buprenorphine by the enzyme cytochrome P450 3A4 (CYP3A4). Norbuprenorphine is a potent opioid receptor agonist, with a high affinity for the mu-opioid receptor (MOR), delta-opioid receptor (DOR), and kappa-opioid receptor (KOR).

Pharmacology

Norbuprenorphine exhibits a different pharmacological profile compared to its parent compound, buprenorphine. While buprenorphine acts as a partial agonist at the mu-opioid receptor, norbuprenorphine is a full agonist at this receptor. This difference in receptor activity contributes to the distinct effects and side effects observed with norbuprenorphine.

Receptor Binding

Norbuprenorphine has a high affinity for the mu-opioid receptor, delta-opioid receptor, and kappa-opioid receptor. It also binds to the nociceptin receptor (NOP), although with lower affinity. The binding affinities (Ki values) for these receptors are as follows:

• Mu-opioid receptor: 0.9 nM
• Delta-opioid receptor: 2.6 nM
• Kappa-opioid receptor: 39 nM
• Nociceptin receptor: 360 nM

Effects

Due to its full agonist activity at the mu-opioid receptor, norbuprenorphine can produce significant analgesia, respiratory depression, and euphoria. However, it is also associated with a higher risk of opioid-induced hyperalgesia and tolerance compared to buprenorphine. Norbuprenorphine's activity at the kappa-opioid receptor may contribute to dysphoria and psychotomimetic effects.

Metabolism

Norbuprenorphine is primarily metabolized in the liver. The main metabolic pathway involves glucuronidation by the enzyme uridine 5'-diphospho-glucuronosyltransferase (UGT). The resulting metabolite, norbuprenorphine-3-glucuronide, is excreted in the urine and bile.

Clinical Significance

The presence of norbuprenorphine in the body can influence the overall pharmacological effects of buprenorphine treatment. It is important to consider the activity of norbuprenorphine when evaluating the efficacy and safety of buprenorphine in clinical settings, particularly in the management of opioid dependence and chronic pain.

See Also

• Buprenorphine
• Opioid receptor
• Cytochrome P450 3A4
• Analgesia
• Opioid dependence