Background and Purpose The μ-opioid receptor (μ receptor) is the primary target for opioid analgesics. 7-transmembrane (TM) 6TM μ isoforms mediate inhibitory excitatory cellular effects. Here, we developed compounds selective 6TM- or 7TM-μ receptors to further our understanding of pharmacodynamic properties receptors. Experimental Approach We performed virtual screening ZINC Drug Now library us...

Antagonistic properties of buprenorphine for and -opioid receptors were characterized in -endorphinand [D-Ala,NMe-Phe,Gly-ol]-enkephalin (DAMGO)-induced antinociception, respectively, with the tail-flick test in male ICR mice. -Opioid receptor agonist -endorphin (0.1–1 g), -opioid receptor agonist DAMGO (0.5–20 ng), or buprenorphine (0.1–20 g) administered i.c.v. dose dependently produced antin...

Neuropeptide FF (NPFF) is known to be an endogenous opioid-modulating peptide. Nevertheless, very few researches focused on the interaction between NPFF and endogenous opioid peptides. In the present study, we have investigated the effects of NPFF system on the supraspinal antinociceptive effects induced by the endogenous µ-opioid receptor agonists, endomorphin-1 (EM-1) and endomorphin-2 (EM-2)...

Opioid drugs produce their pharmacological effects by activating inhibitory guanine nucleotide-binding regulatory protein-linked mu, delta, and kappa opioid receptors. One major effector for these receptors is adenylyl cyclase, which is inhibited upon receptor activation. However, little is known about which of the ten known forms of adenylyl cyclase are involved in mediating opioid actions. He...

BACKGROUND Selective serotonin reuptake inhibitors (SSRIs) have been widely used and are a major therapeutic advance in psychopharmacology. However, their pharmacology is quite heterogeneous. The SSRI fluvoxamine, with sigma-1 receptor agonism, is shown to potentiate nerve-growth factor (NGF)-induced neurite outgrowth in PC 12 cells. However, the precise cellular and molecular mechanisms underl...

Introduction: The analgesic efficacy and side effects of opioid medications show great inter-individual differences. Genetic studies have indicated that this difference is considerably associated with the relationship between receptor. Therefore, in study it was aimed to investigate effect A118G polymorphism on postoperative tramadol consumption opioid-related side-effects after gynecological s...

The sigma (sigma) receptor and its agonists have been implicated in a myriad of cellular functions, biological processes and diseases. Whereas the precise molecular mechanism(s) of sigma receptors and their involvement in cancer cell biology have not been elucidated, recent work has started to shed some light on these issues. A molecular model has been proposed for the cloned sigma1 receptor; t...

We evaluated the effects of s1-receptor inhibition on m-opioid– induced mechanical antinociception and constipation. s1-Knockout mice exhibited marked mechanical antinociception in response to several m-opioid analgesics (fentanyl, oxycodone, morphine, buprenorphine, and tramadol) at systemic (subcutaneous) doses that were inactive in wild-type mice and even unmasked the antinociceptive effects...

G proteins couple delta opioid receptors to multiple cellular effector systems and are critical components of the delta opioid signal transduction cascade. To investigate the physical association of delta opioid receptors with G proteins, the cloned mouse delta opioid receptor was solubilized, and the G proteins associated with the receptor were identified through coimmunoprecipitation of the r...

Recent studies propose that sigma site ligands antagonize N-methyl-D-aspartate (NMDA) receptors by either direct, or indirect mechanisms of inhibition. To investigate this question further we used electrical recordings to assay actions of seventeen structurally diverse sigma site ligands on three diheteromeric subunit combinations of cloned rat NMDA receptors expressed in Xenopus oocytes: NR1a ...