Norbuprenorphine-3-glucuronide (N3G) 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
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 ...
(K
i = 300 nM) and the
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 = 18 μM), but not for the
μ- or
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 ...
s.
Whether N3G 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 ...
or
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 two respective sites has yet to be determined.
In animals, N3G has 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, ...
, decreased
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 ...
, and a small amount 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 ...
, properties which are consistent with the effects of κ-opioid receptor agonists.
In addition, N3G has been found to reduce
tidal volume
Tidal volume (symbol VT or TV) is the volume of air moved into or out of the lungs during a normal breath. In a healthy, young human adult, tidal volume is approximately 500 ml per inspiration or 7 ml/kg of body mass.
Mechanical vent ...
but not
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 ...
.
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
buprenorphine-3-glucuronide
Buprenorphine-3-glucuronide (B3G) is a major active metabolite of the opioid modulator buprenorphine. It has affinity for the μ-opioid receptor (Ki = 4.9 (± 2.7) pM), δ-opioid receptor (Ki = 270 nM), and nociceptin receptor (Ki = 36 μM), but ...
, N3G 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 ...
.
However, due to its highly
hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press.
In contrast, hydrophobes are no ...
nature, N3G nonetheless passes the
blood-brain-barrier in only very small amounts.
See also
*
Morphine-3-glucuronide
Morphine-3-glucuronide is a metabolite of morphine produced by UGT2B7. It is not active as an opioid receptor, opioid agonist, but does have some action as a convulsant, which does not appear to be mediated through opioid receptors, but rather th ...
References
4,5-Epoxymorphinans
Phenols
Tertiary alcohols
Ethers
Glucuronide esters
Kappa-opioid receptor agonists
Opioid metabolites
Peripherally selective drugs
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