Buprenorphine-3-glucuronide (B3G) is a major

active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...

of the opioid modulator

buprenorphine Buprenorphine is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous and subcutaneous), as a skin patch (transdermal), ...

. It has

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

for the

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical � ...

(K_i = 4.9 (± 2.7) pM),

δ-opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous lig ...

(K_i = 270 nM), and

nociceptin receptor The nociceptin opioid peptide receptor (NOP), also known as the nociceptin/orphanin FQ (N/OFQ) receptor or kappa-type 3 opioid receptor, is a protein that in humans is encoded by the ''OPRL1'' (opioid receptor-like 1) gene. The nociceptin receptor ...

(K_i = 36 μM), but not for the

κ-opioid receptor The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP, is a G protein-coupled receptor that in humans is encoded by the ''OPRK1'' gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind op ...

. Whether B3G acts as an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

of each of the former three respective sites has yet to be determined. In rats, at the doses assayed, B3G has been found to produce a small degree of

antinociception An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It i ...

, and similarly to buprenorphine in these assays, has not been found to produce

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

, reduce

locomotion Locomotion means the act or ability of something to transport or move itself from place to place. Locomotion may refer to: Motion * Motion (physics) * Robot locomotion, of man-made devices By environment * Aquatic locomotion * Flight * Locomo ...

, or decrease

respiratory rate The respiratory rate is the rate at which breathing occurs; it is set and controlled by the respiratory center of the brain. A person's respiratory rate is usually measured in breaths per minute. Measurement The respiratory rate in humans is mea ...

. Of all of the active metabolites of buprenorphine, B3G is thought to be the most similar to the parent drug. Unlike

norbuprenorphine 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 ...

, but similarly to buprenorphine (and

norbuprenorphine-3-glucuronide Norbuprenorphine-3-glucuronide (N3G) is a major active metabolite of the opioid modulator buprenorphine. It has affinity for the κ-opioid receptor (Ki = 300 nM) and the nociceptin receptor (Ki = 18 μM), but not for the μ- or δ-opioid recept ...

), B3G is not a substrate for

P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...

, and hence may cross the blood-brain-barrier significantly.

References

Opioid metabolites 4,5-Epoxymorphinans Catechol ethers Tertiary alcohols Secondary alcohols Oripavines Glucuronide esters {{Analgesic-stub

See also

References