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  • analgesia
  • 1,2 To minimize such undesirable effects, the clinical concept of balanced or multimodal analgesia proposes to use a combination of analgesics to provide better pain relief and to minimize the side effects of each drug. (asahq.org)
  • 10 Opioid analgesia may also affect other aspects of the immune response: morphine inhibits production of proinflammatory cytokines by monocytes and inhibits interleukin-2 transcription in activated T lymphocytes. (asahq.org)
  • naloxone
  • Naloxone was able to block the effect of morphine on COS-1 transfected cells. (jimmunol.org)
  • Using guanosine 5′- O -(3-[ 35 S]thio)triphosphate ([ 35 S]GTPγS) binding and adenylyl cyclase activity assay in brain homogenates, we demonstrated that morphine pretreatment of mice enhanced basal MOR signaling in mouse brain homogenates and, moreover, caused persistent changes in the effects of naloxone and naltrexone, antagonists that elicit severe withdrawal in dependent subjects. (aspetjournals.org)
  • Naloxone and naltrexone suppressed basal [ 35 S]GTPγS binding (acting as "inverse agonists") only after morphine pretreatment, but not in drug-naive animals. (aspetjournals.org)
  • Moreover, naloxone and naltrexone stimulated adenylyl cyclase activity in striatum homogenates only after morphine pretreatment, by reversing the inhibitory effects of basal MOR activity. (aspetjournals.org)
  • After cessation of morphine treatment, the time course of inverse naloxone effects on basal MOR signaling was similar to the time course of naltrexone-stimulated narcotic withdrawal over several days. (aspetjournals.org)
  • Second, morphine pretreatment affects the antagonist properties of naloxone and naltrexone. (aspetjournals.org)
  • opioids
  • CHRONIC administration of opioids, in particular morphine, induces tolerance in both humans and animals. (asahq.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)
  • 1 Several retrospective studies have shown a reduced incidence of cancer recurrence after regional anesthesia (epidural, intrathecal, paravertebral) and reduced doses of opioids after surgery for breast, prostate, and colon cancer or melanoma, 2 - 4 although other groups have reported less robust association. (asahq.org)
  • Although related to each other, the sequences of endomorphin-1 (Tyr-Pro-Trp-Phe-NH 2 ) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH 2 ) are quite distinct from traditional opioids in which the first four amino acids are Tyr-Gly-Gly-Phe followed by either methionine or leucine. (aspetjournals.org)
  • From an additional 10 samples found to contain other opioids, 5 were correctly scored positive. (aaccjnls.org)
  • In Europe and North America, highly potent synthetic opioids, which mimic the effects of heroin and morphine, are a growing health threat ( 1 - 4 ). (aaccjnls.org)
  • Thirty-three new synthetic opioids were detected in Europe between 2009 and 2017 ( 5 ). (aaccjnls.org)
  • These synthetic opioids were initially explored by research groups or pharmaceutical companies for their potential medicinal use, but they have recently found their way to the illicit drug market ( 1 - 4 ). (aaccjnls.org)
  • These new synthetic opioids are a major public health concern owing to their high potency, ease of accessibility over the internet, and distribution into the regular street heroin supply, where they are often mixed with or substituted for heroin, leading to life-threatening respiratory depression and death ( 1 - 4 ). (aaccjnls.org)
  • However, opioids such as morphine are limited in their function due to the development of tolerance and physical dependence. (aspetjournals.org)
  • evaluated the effects of the K ATP opener cromakalim administered (i.c.v.) on the enhancement of the antinociceptive effects of various opioids, including morphine. (aspetjournals.org)
  • rats
  • Thus, to test the proposed hypothesis, rats were treated with ketamine or morphine alone or with the combination of both drugs, and then submitted to the capsaicin orofacial test. (asahq.org)
  • demonstrated that deprivation-induced feeding in rats was maximally reduced by an AS ODN probe directed against exon 2 of the KOP gene, an effect complementary to κ antagonist effects, whereas probes directed against exons 2, 3, or 4 of the MOP gene, exon 1 of the DOP gene, and exon 1 of the NOP gene resulted in modest reductions in deprivation-induced intake. (aspetjournals.org)
  • In brains from heroin self-administering rats, decreased μ opioid-stimulated [ 35 S]GTPγS binding was observed in periaqueductal gray, locus coeruleus, lateral parabrachial nucleus, and commissural nucleus tractus solitarius, as previously observed in chronic morphine-treated animals. (jneurosci.org)
  • mice
  • In CXBK mice, which are insensitive to supraspinal morphine, neither endomorphin was active, consistent with a mu mechanism of action. (aspetjournals.org)
  • ICR and Swiss-Webster mice were rendered tolerant to morphine by pellet implantation and were withdrawn by pellet removal. (aspetjournals.org)
  • The ED 50 for Swiss-Webster mice shifted from 13 to 451 mg/kg and thus they were more tolerant to morphine than ICR mice (ED 50 shift from 12 to 120 mg/kg). (aspetjournals.org)
  • Swiss-Webster mice were also dependent to morphine only when the morphine pellet was in place, unlike ICR mice, which were dependent for 48 h after morphine pellet removal. (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)
  • Both strains of mice remained tolerant for 2 days after spontaneous withdrawal from morphine. (aspetjournals.org)
  • However, the only increases in the B max and K D of glyburide were observed in Swiss-Webster mice that were highly tolerant to morphine. (aspetjournals.org)
  • Ozgene mice can be found in 31 different countries on 5 continents from small academic institutions to multinational pharmaceutical companies. (ozgene.com)
  • In this study, we tested basal MOR-signaling activity in brain tissue from untreated and morphine-pretreated mice, in comparison to antagonist-induced withdrawal in morphine-dependent mice. (aspetjournals.org)
  • analgesics
  • In the search for alternative analgesics to morphine, research interests have focused on modifications of well known alkaloids, including the oripavines. (aspetjournals.org)
  • desensitization
  • 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)
  • Morphine induced minimum I K desensitization in both rat groups. (uky.edu)
  • doses
  • In contrast, morphine delivered by percutaneous injections at S1-S2 had only a modest effect on thermal escape, even at higher doses. (jneurosci.org)
  • peptide
  • Endomorphin-1 and endomorphin-2 were synthesized at our institution's Microchemistry Facility, purified by high-performance liquid chromatography, their structures verified by mass spectroscopy and the peptide content (58% for endomorphin-1 and 74% for endomorphin-2) determined by Rockefeller University's Protein Technology Center. (aspetjournals.org)
  • antagonist
  • In assays measuring G-protein activation, TIPP failed to stimulate guanosine 5′- O -(3-[ 35 S]thio)triphosphate ([ 35 S]GTPγS) binding in membrane preparations, which is consistent with an antagonist profile. (aspetjournals.org)
  • neurons
  • The requirement for DA in expression of morphine CPP supports the hypothesis that enhanced firing of VTA dopaminergic neurons contributes to the positive motivational actions of MOR agonists. (jneurosci.org)
  • A dye (DiI), placed in small cavities drilled in rat molars ∼1 week before harvesting the trigeminal ganglia, is transported to the cell body, where its fluorescence distinguishes tooth-pulp afferents from other dissociated trigeminal sensory neurons (Fig. 2 ). (jneurosci.org)
  • antagonism
  • However, the significant reductions in deprivation-induced feeding following antisense probes directed against either exons 2, 4, 7, 8, or 13 of the MOP gene were modest compared with μ antagonism, suggesting a role for multiple μ-mediated mechanisms. (aspetjournals.org)
  • laboratory
  • Our laboratory has demonstrated the presence of basal MOR signaling activity in various tissues in cell culture (Wang et al. (aspetjournals.org)
  • saline
  • 13 ). Moreover, in recent work with serial magnetic resonant imaging in dogs, substitution of saline for morphine after the development of a granuloma led to a regression of the granuloma and that formation was dependent on the concentration, not the dose, of morphine. (asahq.org)
  • naltrexone
  • In morphine-treated monkeys discriminating naltrexone, thienorphine, and U50,488 neither substituted for nor modified the naltrexone discriminative stimulus. (aspetjournals.org)
  • protein
  • the correlation was improved when corrected for protein binding ( r 2 = 0.995). (aspetjournals.org)
  • 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)
  • drugs
  • GPCRs account for up to 50% of currently marketed drugs [ 1 - 4 ] and continue to be the focus of intense research in drug development. (stonel.info)
  • Drugs such as morphine that are agonists at the MOPr are of great therapeutic importance in the management of pain and are also highly significant in terms of their abuse potential. (aspetjournals.org)