AT-076 is a so-called
opioid "pan" antagonist and is the first reasonably balanced
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 ...
known of all four
opioid receptor types.
It acts as a
silent antagonist of all four of the opioid receptors, behaving as a
competitive antagonist
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...
of 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 Π...
(K
i = 1.67 nM) and
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 ligan ...
(K
i = 19.6 nM) and as a
noncompetitive antagonist
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...
of 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 = 1.14 nM) and
nociceptin receptor (K
i = 1.75 nM).
AT-076 was derived from the selective κ-opioid receptor antagonist
JDTic
JDTic is a selective, long-acting ("inactivating") antagonist of the κ-opioid receptor (KOR). JDTic is a 4-phenylpiperidine derivative, distantly related structurally to analgesics such as pethidine and ketobemidone, and more closely to the ...
via removal of the 3,4-dimethyl group of the ''trans''-(3''R'',4''R'')-dimethyl-4-(3-hydroxyphenyl)piperidine antagonist scaffold, which increased
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 Partn ...
for the nociceptin receptor by 10-fold and for the μ- and δ-opioid receptors by 3-6-fold.
See also
*
AT-121
*
Cebranopadol
Cebranopadol (developmental code GRT-6005) is an opioid analgesic of the benzenoid class which is currently under development internationally by Grünenthal, a Germany, German pharmaceutical company, and its partner Depomed, a pharmaceutical comp ...
*
Buprenorphine
*
BU09059
BU09059 is a potent, selective, short-acting (non-"inactivating") antagonist of the κ-opioid receptor (KOR). It was derived from the irreversible (long-acting) KOR antagonist JDTic in search of an antagonist with a reversible profile of inact ...
References
4-Phenylpiperidines
Carboxamides
Delta-opioid receptor antagonists
Kappa-opioid receptor antagonists
Mu-opioid receptor antagonists
Nociceptin receptor antagonists
Phenols
Synthetic opioids
Tetrahydroisoquinolines
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