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 main enemy or rival of the protagonist and is often depicted as a villain.opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostati ...

types. It acts as a

silent 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 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 alpha subunit, Gi/G0 and has enkephalins as it ...

(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 for its ligand ketazocine, 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 re ...

(K_i = 1.14 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 recepto ...

(K_i = 1.75 nM). AT-076 was derived from the selective κ-opioid receptor antagonist JDTic 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 Pa ...

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 3-Hydroxyphenyl compounds Synthetic opioids Tetrahydroisoquinolines {{analgesic-stub

See also

References