The natural stilbene pawhuskin A has been shown to function as an opioid receptor antagonist, with preferential binding to the κ receptor. This finding encouraged assembly of a set of analogues to probe the importance of key structural features. Assays on these compounds determined that one (compound 29) shows potent opioid receptor binding activity and significantly improved selectivity for th...

The three opioid receptors (μ, δ, and κ) are important targets for pain management and have also shown promise as targets for treatment of addiction and mood disorders. In the past, research in the field commonly focused on analysis of structure-activity relationships (SAR) and ligands’ conformational preferences. Recently, advancements permitted determination of crystal structures for each of ...

Substantial evidence has been accumulated which suggests that opioid delta receptors may be distinguished on the basis of their involvement in the modulation (i.e., increase or decrease in potency) of mu-mediated antinociception. On this basis, it has been hypothesized that some opioid delta receptors exist within a functional complex with mu receptors (delta complexed (delta cx) receptors) whi...

Although opioids are highly effective for the treatment of pain, they are also known to be intensely addictive. There has been a massive research investment in the development of opioid analgesics, resulting in a plethora of compounds with varying affinity and efficacy at all the known opioid receptor subtypes. Although compounds of extremely high potency have been produced, the problem of tole...

synthesized from dipeptidyl chloromethyl ketones or methyl ketones. According to this novel procedure, various functional groups could be introduced into positions 3 and 6 of 1,2-dihydropyrazin-2-one by using appropriate amino acids (Chart 2). It had been assumed that the formation of the 1,2-dihydropyrazin-2-one ring from dipeptidyl chloromethyl ketones proceeded according to the mechanism sho...

Since their first occurrence in 2008, a rapid increase of new psychoactive substances (NPS) on the recreational drug market has been observed. One class NPS are synthetic opioids, which poses health risk due to high affinity and potency most these compounds for opioid receptors. Four receptor subtypes known, mü-opioid (MOR), delta-opioid (DOR), kappa-opioid (KOR) nociceptin receptor, G protein-...

On the basis of pharmacological, behavioral and biochemical studies, opioid receptors have been classified into three major types, μ, δ and κ, belonging to the family of the G protein-coupled receptors. All three receptor types are expressed in the central and peripheral nervous systems of both animals and human. Receptor type selective opioid agonists and antagonists are of interest both as ph...

Opioid analgesics are clinically used to relieve severe pain in acute postoperative and cancer pain, also the long term chronic pain. The analgesic action is mediated by μ-, δ-, κ-receptors, but currently, with few exceptions for k-agonists, μ-agonists only ones therapy. Previously synthesized compounds diazotricyclodecane cores (DTDs) have shown their effectiveness binding opioid receptors. Fo...

Most classical preclinical tests to predict antidepressant activity were initially developed to detect compounds that influenced noradrenergic and/or serotonergic activity, in accordance with the monoaminergic hypothesis of depression. However, central opioid systems are also known to influence the pathophysiology of depression. While the tail suspension test (TST) is very sensitive to several ...