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 � ...

(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.

References

4-Phenylpiperidines Carboxamides Delta-opioid receptor antagonists Kappa-opioid receptor antagonists Mu-opioid receptor antagonists Nociceptin receptor antagonists Phenols Synthetic opioids Tetrahydroisoquinolines {{analgesic-stub

See also

References