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  • whereas
  • Our results show that overall there is a very good correlation between efficacy for G protein activation and arrestin-3 recruitment, whereas a few agonists, in particular endomorphins 1 and 2, display apparent bias toward arrestin recruitment. (aspetjournals.org)
  • opioids
  • Opioids produce their physiological effects by acting upon opioid receptors. (aspetjournals.org)
  • 2-4 Although the occurrence of severe respiratory depression and related deaths in the treatment of acute and perioperative pain seems constant over the years (with an incidence of at least 0.5%), 1 , 5 over the last decade there has been a dramatic surge in fatalities from prescription opioids in chronic pain patients due to a dramatic increase in opioid consumption. (asahq.org)
  • The μ-opioid receptor (MOR) is a GPCR that mediates the effects of endogenous opioids and opioid analgesics, such as morphine. (sciencemag.org)
  • chronic
  • Chronic μ-opioid agonist treatment leads to dependence with withdrawal on removal of agonist. (aspetjournals.org)
  • Chronic use of μ-opioid agonists leads to dependence, resulting in a withdrawal syndrome upon cessation of clinical treatment or illicit use. (aspetjournals.org)
  • Glyburide binding increased during chronic morphine treatment in Swiss-Webster mice by over 2-fold (from 294 to 635 fmol/mg of protein). (aspetjournals.org)
  • However, the mechanisms responsible for the NMDA receptor plasticity, particularly in response to chronic MOR activation, are unclear and understudied. (asahq.org)
  • desensitization
  • The results indicate that desensitization protects receptors from irreversible antagonism with β-CNA. (aspetjournals.org)
  • The amount of desensitization was measured as the decrease in current during a 10-min application of a saturating agonist concentration and was a good predictor of the extent of receptor protection from irreversible inactivation with β-CNA. (aspetjournals.org)
  • There was, however, no recovery of MOR-mediated current with time after treatment with agonists that did not cause desensitization, such as oxycodone. (aspetjournals.org)
  • These results demonstrate that desensitization prevents irreversible inactivation of receptors by β-CNA. (aspetjournals.org)
  • It remains unclear whether differences in agonist-specific desensitization affect the rate and extent of recovery of MOR signaling. (aspetjournals.org)
  • B, β-CNA (500 nM, 2 min) was applied immediately after ME (30 μM, 10 min) induced desensitization, and recovery was again measured with ME test pulses at 5 and 45 min. (aspetjournals.org)
  • indicating that opioid desensitization may occur at different levels or sites of the receptor-G-protein-channel pathway. (jneurosci.org)
  • methadone
  • Testing of methadone and its isomers allowed us to take advantage of the stereoselectivity of the μ-agonist effect. (asahq.org)
  • 1999
  • However, because this property is both a drug- and tissue-dependent quantity, its value for an agonist can vary from tissue to tissue ( Christopoulos and El-Fakahany, 1999 ), which can confound interpretation. (aspetjournals.org)
  • 1999;13(2):107-9. (ketamine.co.uk)
  • efficacy
  • Perhaps a more useful measure of efficacy is relative intrinsic efficacy ( Furchgott and Bursztyn, 1967 ), which enables comparison of responses produced by equivalent fractional occupancy of the receptors by different agonists in the same tissue. (aspetjournals.org)
  • These studies showed that thienorphine is a long-acting low-efficacy κ-opioid receptor agonist, producing moderate antinociceptive effects, potent rate-decreasing effects, and directly observable signs that resemble the signs produced by prototypic κ-opioid agonists. (aspetjournals.org)
  • regulate
  • These results provide a cellular mechanism for the opposing behavioral effects of KOR and MOR agonists and shed light on how KORs might regulate the motivational effects of both natural rewards and addictive drugs. (jneurosci.org)