Conversely, buprenorphine behaves like a partial agonist of the MOR with respect to respiratory depression.Buprenorphine is also known to bind to with high affinity and antagonize the putative ε-opioid receptor.Full analgesic efficacy of buprenorphine requires both exon 11- and exon 1-associated μ-opioid receptor splice variants.The active metabolites of buprenorphine are not thought to be clinically important in its CNS effects.In positron emission tomography (PET) imaging studies, buprenorphine was found to decrease whole-brain MOR availability due to receptor occupancy by 41% (i.e., 59% availability) at 2 mg, 80% (i.e., 20% availability) at 16 mg, and 84% (i.e., 16% availability) at 32 mg.

Other actions
Unlike some other opioids and opioid antagonists, buprenorphine binds only weakly to and possesses little if any activity at the sigma receptor.Buprenorphine also blocks voltage-gated sodium channels via the local anesthetic binding site, and this underlies its potent local anesthetic properties.Similarly to various other opioids, buprenorphine has also been found to act as an agonist of the toll-like receptor 4, albeit with very low affinity. Pharmacokinetics
Buprenorphine is metabolized by the liver, via CYP3A4 (also CYP2C8 seems to be involved) isozymes of the cytochrome P450 enzyme system, into norbuprenorphine (by N-dealkylation). The glucuronidation of buprenorphine is primarily carried out by UGT1A1 and UGT2B7, and that of norbuprenorphine by UGT1A1 and UGT1A3. These glucuronides are then eliminated mainly through excretion into bile. The elimination half-life of buprenorphine is 20 to 73 hours (mean 37 hours).
In the United States, it was rejected for the treatment of transthyretin amyloidosis with polyneuropathy because the Food and Drug Administration saw insufficient evidence for its efficacy.Tafamidis can also be used to treat transthyretin amyloidosis with cardiomyopathy. It was approved for the treatment of this form of the disease in the United States in 2019 and in the European Union in 2020. In the United States, there are two approved preparations: tafamidis meglumine (Vyndaqel) and tafamidis (Vyndamax). The two preparations have the same active moiety, tafamidis, but they are not substitutable on a milligram to milligram basis.Tafamidis (Vyndamax) and tafamidis meglumine (Vyndaqel) were approved for medical use in Australia in March 2020. References
Further reading
Adams D (March 2013). "Recent advances in the treatment of familial amyloid polyneuropathy". Ther Adv Neurol Disord. 6 (2): 129–39. doi:10.1177/1756285612470192. PMC 3582309. PMID 23483184. Coelho T, Maia LF, Martins da Silva A,  et al. (August 2012). "Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial". Neurology. 79 (8): 785–92. doi:10.1212/WNL.0b013e3182661eb1. PMC 4098875. PMID 22843282. External links
"Tafamidis". Drug Information Portal. U.S. National Library of Medicine. "Tafamidis meglumine". Drug Information Portal. U.S. National Library of Medicine.