• ligands
  • It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice [ PMID: 12679517 ]. (ebi.ac.uk)
  • Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [ PMID: 2111655 , PMID: 2830256 , PMID: 8386361 ]. (ebi.ac.uk)
  • Unlike other known opioid-receptor ligands, salvinorin A is not an alkaloid as it does not contain a basic nitrogen atom. (wikipedia.org)
  • Through activation of the KOR, dynorphins, opioid peptides that are the endogenous ligands of the KOR and that can, in many regards, be figuratively thought of as functional inverses of the morphine-like, euphoric and stress-inhibiting endorphins, induce dysphoria and stress-like responses in both animals and humans, as well as psychotomimetic effects in humans, and are thought to be essential for the mediation of the dysphoric aspects of stress. (wikipedia.org)
  • Trevena Inc is a clinical stage biopharmaceutical company, headquartered in Chesterbrook, Pennsylvania, USA, and is involved in the discovery and development of G-protein coupled receptors (GPCR) biased ligands. (wikipedia.org)
  • Trevena has received funding from the Michael J. Fox Foundation to explore the potential for delta opioid receptor biased ligands to treat Parkinson's disease. (wikipedia.org)
  • morphine-induced
  • mE7M-B6 mutant mice lost morphine-induced receptor desensitization in the brain stem and hypothalamus, consistent with exon 7 involvement in morphine tolerance. (jci.org)
  • In cell-based studies, exon 7-associated variants shifted the bias of several mu opioids toward β-arrestin 2 over G protein activation compared with the exon 4-associated variant, suggesting an interaction of exon 7-associated C-terminal tails with β-arrestin 2 in morphine-induced desensitization and tolerance. (jci.org)
  • The canonical MOR1 isoform is responsible for morphine-induced analgesia, whereas the alternatively spliced MOR1D isoform (through heterodimerization with the gastrin-releasing peptide receptor) is required for morphine-induced itching. (wikipedia.org)
  • Imax = 29%) with lower relative intrinsic activity and marked antagonistic potential (including the ability to antagonize morphine-induced effects and induce opioid withdrawal in opioid-dependent individuals). (wikipedia.org)
  • proteins
  • The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. (ebi.ac.uk)
  • Once isolated, the receptor and the proteins bound to it may be identified by mass spectrometry. (newswise.com)
  • Expression of opioid receptor proteins is controlled by extensive transcriptional and post-transcriptional processing. (nih.gov)
  • This includes downregulation of MOR gene expression, so the number of receptors presented on the cell surface is actually reduced, as opposed to the more short-term desensitisation induced by β-arrestins or RGS proteins. (wikipedia.org)
  • affinity
  • This suggests that substitution at both the 3 and 4 positions of the piperidine ring introduces steric hindrance which prevents μ-opioid affinity from increasing much further. (wikipedia.org)
  • Another side effect which is characteristic of fentanyl and its derivatives is their tendency to rapidly induce tolerance, due to their high binding affinity triggering rapid internalization of chronically activated opiate receptors. (wikipedia.org)
  • It has a high affinity for the receptor, indicated by the low dissociation constant of 1.0 nanomolar (nM). (wikipedia.org)
  • pathways
  • While a variety of prescribed or over-the-counter (OTC) medications are available for pain management, opioid medications, especially those acting on the m-opioid receptor (mOR)and related pathways, have proven to be the most effective, despite some serious side effects including respiration depression, pruritus, dependence, and constipation. (epfl.ch)
  • antagonism
  • To investigate the effects of chronic mu-opioid antagonism in the nucleus accumbens core or shell on intake of a palatable diet, and the development of diet-induced obesity in rats. (pubmedcentralcanada.ca)
  • methadone
  • LAAM is indicated as a second-line treatment for the treatment and management of opioid dependence if patients fail to respond to drugs like methadone or buprenorphine. (wikipedia.org)
  • selectively
  • These findings suggest that serotonin uptake inhibitors can selectively enhance the antinociceptive effects of mu agonists in nonhuman primates. (aspetjournals.org)
  • analgesia
  • The long duration and high lipophilicity of lofentanil has been suggested as an advantage for certain types of analgesia, but the main application for lofentanil at the present time is research into opioid receptors. (wikipedia.org)
  • acute
  • Trevena's leading drug candidate is Oliceridine (TRV130), a G protein-biased ligand binding to the mu opioid receptor for the intravenous treatment of acute moderate-to-severe post-operative pain. (wikipedia.org)
  • Trevena's developed TRV027 for acute heart failure, targets the angiotensin receptor utilizing beta-arrestin bias, an approach that has shown numerous beneficial cardiovascular and renal actions in preclinical species. (wikipedia.org)
  • effects
  • Serotonergic systems also modulate nociception, and serotonin uptake inhibitors may be useful as adjuncts to enhance analgesic effects and/or attenuate undesirable effects of mu agonists. (aspetjournals.org)
  • Clomipramine was inactive alone and did not alter effects of mu agonists. (aspetjournals.org)
  • These effects of serotonin uptake inhibitors may be dependent on the proportion of the serotonin uptake inhibitor and the efficacy of the mu agonist. (aspetjournals.org)
  • As such, its effects do not rely on the cognate membrane receptors. (wikipedia.org)
  • It is a useful drug for the treatment of pain, but side effects such as dizziness limit its clinical application, and it can produce opioid withdrawal syndrome in patients already dependent on other opioids. (wikipedia.org)
  • This suggests that the D2 receptor may also play an important role in its effects. (wikipedia.org)
  • serotonin
  • In addition to its opioid actions, dezocine has been found to act as a serotonin-norepinephrine reuptake inhibitor (SNRI), with pIC50 values of 5.86 for the serotonin transporter (SERT) and 5.68 for the norepinephrine transporter (NET). (wikipedia.org)
  • Salvinorin A has no action at the 5-HT2A serotonin receptor, the principal molecular target responsible for the actions of 'classical' psychedelics such as LSD and mescaline. (wikipedia.org)
  • dependence
  • It was approved in 1993 by the U.S. Food and Drug Administration for use in the treatment of opioid dependence. (wikipedia.org)
  • This unique benefit makes long-term low-dose treatment of chronic pain and/or opioid dependence with dezocine more feasible than with most other opioids. (wikipedia.org)
  • Targeting
  • Other delta opioid-targeting drugs are known to cause seizures, but Trevaga hopes to avoid this with TRV250 by bypassing the β-arrestin pathway. (wikipedia.org)
  • downstream
  • The precise mechanism of action in explanation of their analgesic efficacy is unclear, but it is thought that they indirectly modulate the opioid system in the brain downstream via serotonergic and noradrenergic neuromodulation, among other properties. (wikipedia.org)
  • weak
  • It has been used as a lead compound to derive further analogues, although all compounds in this family are comparatively weak mu agonists. (wikipedia.org)
  • chronic
  • Trevena's pipeline currently includes a clinical stage mu-opioid biased ligand for post-operative pain, and discovery-stage programs for chronic pain, migraine, and Parkinson's disease. (wikipedia.org)
  • mechanism
  • The MOR is the target of opioid drugs like morphine and is an important mechanism for pain regulation in the body. (newswise.com)
  • To elucidate the effect of an opioid on airway smooth muscle relaxant responses and its mechanism of action, we studied canine bronchial segments under isometric conditions in vitro. (aspetjournals.org)