The existence of multiple receptor sites for the psychotomimetic agents phencyclidine (PCP) and some opiate-benzomorphans such as (+)N-allylnormetazocine ([+]SKF 10,047) in the mammalian central nervous system is well documented. These are: 1) sigma/PCP (sigma p) site, which binds both PCP and psychotomimetic opiates but not antipsychotics such as haloperidol, 2) PCP site, which selectively bin...

Compound trans-4-(p-bromophenyl)-4-(dimethylamino)-1-(2-thiophen-2-yl-ethyl)-cyclohexanol (C8813), structurally unrelated to morphine, is a novel analgesic. The present study examined the antinociception, opioid receptor selectivity and in vitro activity of C8813. The antinociceptive activity was evaluated using mouse hot plate and acetic acid writhing tests. In mouse hot plate test, the antino...

Although much has been learned about the mechanisms of ligand selectivity between different opioid receptor subtypes, little is known about the common opioid binding pocket shared by all opioid receptors. The recently discovered orphanin system offers a good opportunity to study the mechanisms involved in the binding of opioid versus nonopioid ligands. In the current study, we adopt a "gain of ...

This presentation will review basic and clinical concepts on pain mechanisms underlying opioid analgesia. It describe the structure, function, cellular signaling of receptors; endogenous exogenous receptor ligands; as well central peripheral sites actions. The also discuss novel opioid-based therapeutic strategies, developed from recently gained knowledge structures signaling, patholo...

Despite mu opioid receptor agonists are the cornerstones of moderate-to-severe acute pain treatment, their effectiveness in chronic pain conditions is controversial. In contrast to mu opioid receptor agonists, a number of studies have reported the effectiveness of delta opioid receptor agonists on neuropathic pain strengthening the idea that delta opioid receptors gain importance when chronic p...

Inhibition of forebrain μ-opioid receptor signaling by low concentrations of rimonabant does not require cannabinoid receptors and directly involves μ-opioid receptors. Micromolar concentrations of rimonabant directly inhibits delta opioid receptor specific ligand binding and agonist-induced G-protein activity. receptor ligand with high in vitro and in vivo agonist efficacy.

We previously reported that the sigma-1 receptor is down-regulated in cardiomyocytes following heart failure in transverse aortic constriction (TAC) mice. In this review, we summarized the anti-hypertrophic action of selective sigma-1 receptor agonist, SA4503 in the hypertrophied cultured cardiomyocytes and discussed its possible mechanism of cardioprotection. Treatment with SA4503 (0.1-1 μM) d...

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...