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Opioid Receptor Agonist (opioid + receptor_agonist)
Selected AbstractsDelta2 -Specific Opioid Receptor Agonist and Hibernating Woodchuck Plasma Fraction Provide Ischemic NeuroprotectionACADEMIC EMERGENCY MEDICINE, Issue 3 2008Meera Govindaswami PhD Abstract Objectives:, The authors present evidence that the , opioid receptor agonist Deltorphin-Dvariant (Delt-Dvar) and hibernating woodchuck plasma (HWP), but not summer-active woodchuck plasma (SAWP), can provide significant neuroprotection from focal ischemia in mice by a mechanism that relies in part on reducing nitric oxide (NO) release in ischemic tissue. Methods:, Cerebral ischemia was produced in wild-type and NO synthase,deficient (NOS,/,) mice by transient, 1-hour middle cerebral artery occlusion (MCAO). Behavioral deficits were determined at 22 hours and infarct volume was assessed at 24 hours after MCAO. Mice were treated with saline or Delt-Dvar at 2.0 and 4.0 mg/kg, or 200 ,L of HWP or SAWP. NOS,/, mice were treated with either saline or Delt-Dvar at 4.0 mg/kg. NO release was determined using an N9 microglial cell line pretreated with ,- or ,-specific opioids and HWP or SAWP prior to activation with lipopolysaccharide and interferon-,. Nitrate in the medium was measured as an indicator of NO production. Results:, Infusion of Delt-Dvar or HWP (but not SAWP) decreased infarct volume and improved behavioral deficits following 1 hour of MCAO and 24 hours of reperfusion. In NOS,/, mice, endothelial NOS+/+ is required to provide Delt-Dvar,induced neuroprotection. Delt-Dvar and HWP dose-dependently decreased NO release in cell culture, while SAWP and other ,- and ,-specific opioids did not. Conclusions:, Delt-Dvar and HWP, but not SAWP, are effective neuroprotectant agents in a mouse model of transient MCAO. In cell culture, the mechanism of this ischemic neuroprotection may rely in part on their ability to block NO release. [source] ChemInform Abstract: New Diarylmethylpiperazines as Potent and Selective Nonpeptidic ,-Opioid Receptor Agonists with Increased in vitro Metabolic Stability.CHEMINFORM, Issue 10 2001Niklas Plobeck Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Cellular Actions Of Opioids And Other Analgesics: Implications For Synergism In Pain ReliefCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2000MacDonald J Christie SUMMARY 1. ,-Opioid receptor agonists mediate their central analgesic effects by actions on neurons within brain regions such as the mid-brain periaqueductal grey (PAG). Within the PAG, ,-opioid receptor-mediated analgesia results from inhibition of GABAergic influences on output projection neurons. We have established that ,-opioid receptor activation in the PAG causes a presynaptic inhibition of GABA release that is mediated by activation of a voltage-dependent K+ channel via 12-lipoxygenase (LOX) metabolites of arachidonic acid. 2. At a cellular level, ,-opioid agonists have also been shown to open inwardly rectifying K+ channels, close voltage-gated Ca2+ channels and presynaptically inhibit glutamatergic synaptic transmission in the PAG. 3. The ,-opioid receptor-mediated presynaptic inhibition of GABAergic transmission was abolished by phospholipase A2 inhibitors and non-specific LOX and specific 12-LOX inhibitors. Cyclo-oxygenase (COX) and specific 5-LOX inhibitors did not reduce the inhibitory effects of ,-opioid agonists. 4. The opioid actions on GABAergic transmission were mimicked by arachidonic acid and 12-LOX metabolites, but not 5-LOX metabolites. The efficacy of ,-opioids was enhanced synergistically by treatment of PAG neurons with inhibitors of the other major enzymes responsible for arachidonic acid metabolism, COX and 5-LOX. 5. These results explain a previously described analgesic action of COX inhibitors in the central nervous system that was both independent of prostanoid release and inhibited by opioid receptor antagonists and they also explain the synergistic interaction of opioids with COX inhibitors. These findings also suggest new avenues for the development of centrally active analgesic agents involving combinations of lowered doses of opioids and specific 5-LOX inhibitors. [source] A unique binding epitope for salvinorin A, a non-nitrogenous kappa opioid receptor agonistFEBS JOURNAL, Issue 9 2006Brian E. Kane Salvinorin A is a potent kappa opioid receptor (KOP) agonist with unique structural and pharmacological properties. This non-nitrogenous ligand lacks nearly all the structural features commonly associated with opioid ligand binding and selectivity. This study explores the structural basis to salvinorin A binding and selectivity using a combination of chimeric and single-point mutant opioid receptors. The experiments were designed based on previous models of salvinorin A that locate the ligand within a pocket formed by transmembrane (TM) II, VI, and VII. More traditional sites of opioid recognition were also explored, including the highly conserved aspartate in TM III (D138) and the KOP selectivity site E297, to determine the role, if any, that these residues play in binding and selectivity. The results indicate that salvinorin A recognizes a cluster of residues in TM II and VII, including Q115, Y119, Y312, Y313, and Y320. Based on the position of these residues within the receptor, and prior study on salvinorin A, a model is proposed that aligns the ligand vertically, between TM II and VII. In this orientation, the ligand spans residues that are spaced one to two turns down the face of the helices within the receptor cavity. The ligand is also in close proximity to EL-2 which, based on chimeric data, is proposed to play an indirect role in salvinorin A binding and selectivity. [source] Remifentanil post-conditioning attenuates cardiac ischemia,reperfusion injury via , or , opioid receptor activationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010G. T. C. WONG Background: Ischemic pre- or post-conditioning of the heart has been shown to involve opioid receptors. Remifentanil, an ultra-short-acting selective , opioid receptor agonist in clinical use, pre-conditions the rat heart against ischemia,reperfusion injury. This study investigates whether remifentanil post-conditioning is also cardioprotective. Methods: Remifentanil post-conditioning (5-min infusion at 1, 5, 10 or 20 ,g/kg/min) or ischemic post-conditioning (three cycles of a 10 s reperfusion interspersed with a 10 s ischemia) was induced in an open-chest rat heart model of ischemia and reperfusion injury, in the presence or absence of nor-binaltorphimine, naltrindole or CTOP, specific ,, , and , opioid receptor antagonists, respectively. The same sequence of experiments was repeated in the isolated heart model using the maximal protective dose of remifentanil from the dose,response studies. Results: Both ischemic and remifentanil post-conditioning reduced the myocardial infarct size relative to the control group in both models. This cardioprotective effect for both post-conditioning regimes was prevented by the prior administration of nor-binaltorphimine and naltrindole but not CTOP. The sole administration of the antagonists had no effect on the size of myocardial infarction. Conclusions: These results indicate that remifentanil post-conditioning protects the heart from ischemia,reperfusion injury to a similar extent as of ischemic post-conditioning. This protection involves , and , but not , opioid receptor activation. This drug has great potential as a clinical post-conditioning modality as it can be given in large doses without prolonged opioid-related side effects. [source] Synthesis of N, N -diethyl-4-[phenyl-(piperidin-4-ylidene)methyl]-[carboxy - 14C]benzamide, a potent , opioid receptor agonistJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2003Lars Gawell Abstract The synthesis of carbon-14 labelled N,N -diethyl-4-[phenyl-(piperidin-4-ylidene)methyl]-benzamide is described. The radioisotope is introduced via an aryllithium reaction with 14CO2 to form the labelled acid, which is subsequently transformed into the amide. Copyright © 2002 John Wiley & Sons, Ltd. [source] The oxidation metabolites of endomorphin 1 and its fragments induced by free radicalsJOURNAL OF PEPTIDE SCIENCE, Issue 5 2009Pin Gong Abstract Endomorphin 1 (EM1), an endogenous µ-opioid receptor agonist, acts as a free radical scavenger in vitro and an antioxidant in vivo. The modification of EM1 by ROS and the properties of the OM attracted our attention. In vitro assays were performed via RP-HPLC, spectrophotometric measurements, EPR and amino acid analysis, Schmorl's reaction to define the formation of melanin-like compounds transformed from EM1, collectively named EM1,melanin and by solubility assay, radioligand-binding assay, NADH oxidation, superoxide anion scavenging assay to study some physical and chemical properties of EM1,melanin. Possible pathways of the formation of EM1,melanin were proposed. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] Loperamide and P-glycoprotein inhibition: assessment of the clinical relevanceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2010Joris Vandenbossche Abstract Objectives Loperamide is a peripherally acting , opioid receptor agonist and an avid substrate for P-glycoprotein. This may give rise to drug,drug interactions and increased risk for central adverse effects. The objective of this study was to re-evaluate the predictability of non-clinical data using loperamide as a probe P-glycoprotein substrate. We searched the literature for papers containing data on drug,drug interactions of loperamide-containing products in humans. We also reviewed the internal worldwide safety database of Johnson & Johnson for spontaneous case reports suggestive of a central opioid effect after coadministration of loperamide with a P-glycoprotein inhibitor or substrate. Key findings Only one of the ten studies in our review supported the finding that inhibition of P-glycoprotein is associated with clinically relevant signs or symptoms of central nervous system (CNS) depression/opioid toxicity of loperamide. None of the 25 spontaneous case reports of interest were suggestive of signs or symptoms of CNS depression/opioid toxicity due to coadministration of loperamide and a P-glycoprotein inhibitor or substrate. Summary Based on a review of the literature and a cumulative review of the sponta-neous case reports, there is insufficient evidence that an interaction between loperamide and a P-glycoprotein inhibitor or substrate is associated with clinical symptoms of CNS depression/opioid toxicity when loperamide is taken at the recommended dose. [source] Opioids in the Hypothalamic Paraventricular Nucleus Stimulate Ethanol IntakeALCOHOLISM, Issue 2 2010Jessica R. Barson Background:, Specialized hypothalamic systems that increase food intake might also increase ethanol intake. To test this possibility, morphine and receptor-specific opioid agonists were microinjected in the paraventricular nucleus (PVN) of rats that had learned to drink ethanol. To cross-validate the results, naloxone methiodide (m-naloxone), an opioid antagonist, was microinjected with the expectation that it would have the opposite effect of morphine and the specific opioid agonists. Methods:, Sprague,Dawley rats were trained, without sugar, to drink 4 or 7% ethanol and were then implanted with chronic brain cannulas aimed at the PVN. After recovery, those drinking 7% ethanol, with food and water available, were injected with 2 doses each of morphine or m-naloxone. To test for receptor specificity, 2 doses each of the ,-receptor agonist [d -Ala2,N -Me-Phe4,Gly5 -ol]-Enkephalin (DAMGO), ,-receptor agonist d -Ala-Gly-Phe-Met-NH2 (DALA), or ,-receptor agonist U-50,488H were injected. DAMGO was also tested in rats drinking 4% ethanol without food or water available. As an anatomical control for drug reflux, injections were made 2 mm dorsal to the PVN. Results:, A main result was a significant increase in ethanol intake induced by PVN injection of morphine. The opposite effect was produced by m-naloxone. The effects of morphine and m-naloxone were exclusively on intake of ethanol, even though food and water were freely available. In the analysis with specific receptor agonists, PVN injection of the ,-agonist DALA significantly increased 7% ethanol intake without affecting food or water intake. This is in contrast to the ,-agonist U-50,488H, which decreased ethanol intake, and the ,-agonist DAMGO, which had no effect on ethanol intake in the presence or absence of food and water. In the anatomical control location 2 mm dorsal to the PVN, no drug caused any significant changes in ethanol, food, or water intake, providing evidence that the active site was close to the cannula tip. Conclusions:, The ,-opioid receptor agonist in the PVN increased ethanol intake in strong preference over food and water, while the ,-opioid agonist suppressed ethanol intake. Prior studies show that learning to drink ethanol stimulates PVN expression and production of the peptides enkephalin and dynorphin, which are endogenous agonists for the ,- and ,-receptors, respectively. These results suggest that enkephalin via the ,-opioid system can function locally within a positive feedback circuit to cause ethanol intake to escalate and ultimately contribute to the abuse of ethanol. This is in contrast to dynorphin via the ,-opioid system, which may act to counter this escalation. Naltrexone therapy for alcoholism may act, in part, by blocking the enkephalin-triggered positive feedback cycle. [source] Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horsesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009R. L. LINARDI Methadone hydrochloride is a synthetic ,-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/mass spectrometry at predetermined time points for 24 h, and PK parameters were estimated using a noncompartmental model. Physical effects were observed and recorded by experienced clinicians. No drug toxicity, behavioural or adverse effects were observed in the horses. The disposition of methadone followed first order elimination and a biphasic serum profile with rapid absorption and elimination phases. The PK profile of methadone was characterized by high clearance (Cl/F), small volume of distribution (Vd/F) and short elimination half-life (t1/2). The mean of the estimated t1/2 (SD) for each dose (0.1, 0.2 and 0.4 mg/kg) was 2.2 (35.6), 1.3 (46.1) and 1.5 (40.8), and the mean for the estimated Cmax (SD) was 33.9 (6.7), 127.9 (36.0) and 193.5 (65.8) respectively. [source] Novel pharmacology: asimadoline, a ,-opioid agonist, and visceral sensationNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2008M. Camilleri Abstract, Asimadoline is a potent ,-opioid receptor agonist with a diaryl acetamide structure. It has high affinity for the , receptor, with IC50 of 5.6 nmol L,1 (guinea pig) and 1.2 nmol L,1 (human recombinant), and high selectively with , : , : , binding ratios of 1 : 501 : 498 in human recombinant receptors. It acts as a complete agonist in in vitro assay. Asimadoline reduced sensation in response to colonic distension at subnoxious pressures in healthy volunteers and in irritable bowel syndrome (IBS) patients without alteration of colonic compliance. Asimadoline reduced satiation and enhanced the postprandial gastric volume (in female volunteers). However, there were no significant effects on gastrointestinal transit, colonic compliance, fasting or postprandial colonic tone. In a clinical trial in 40 patients with functional dyspepsia (Rome II), asimadoline did not significantly alter satiation or symptoms over 8 weeks. However, asimadoline, 0.5 mg, significantly decreased satiation in patients with higher postprandial fullness scores, and daily postprandial fullness severity (over 8 weeks); the asimadoline 1.0 mg group was borderline significant. In a clinical trial in patients with IBS, average pain 2 h post- on-demand treatment with asimadoline was not significantly reduced. Post hoc analyses suggest that asimadoline was effective in mixed IBS. In a 12-week study in 596 patients, chronic treatment with 0.5 mg and 1.0 mg asimadoline was associated with adequate relief of pain and discomfort, improvement in pain score and number of pain-free days in patients with IBS-D. The 1.0 mg dose was also efficacious in IBS-alternating. There were also weeks with significant reduction in bowel frequency and urgency. Asimadoline has been well tolerated in human trials to date. [source] Clinical Pharmacology of OxymorphonePAIN MEDICINE, Issue 2009Howard S. Smith MD ABSTRACT Oxymorphone (14-hydroxydihydromorphinone) is primarily a potent ,-opioid receptor agonist with oral immediate-release (IR) and extended-release (ER) formulations approved in the United States in 2006. The oral oxymorphone formulations are roughly three times more potent than oral morphine. It is more lipophilic than morphine and, thus, may more easily cross the blood-brain barrier because it differs from morphine having a ketone-group substituent at the C-6 position. Oxymorphone IR is indicated for the relief of moderate,to severe pain, while oxymorphone ER is indicated for persistent pain. Initial doses (opioid-naïve) are 10,20 mg every 4,6 hours (IR) and 5 mg every 12 hours (ER). Oxymorphone was found not to have any clinically significant cytochrome (CYP)3A4, CPY2C9, or CYP2D6 interactions, thus limiting its potential for causing some of the more common drug,drug interactions via the CYP450 system. The common adverse effects of oxymorphone are consistent with those commonly seen with other opioid, including nausea/vomiting, constipation, pruritis, pyrexia, somnolence, and sedation. [source] In vitro and in vivo pharmacological profile of UFP-512, a novel selective ,-opioid receptor agonist; correlations between desensitization and toleranceBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2007B Aguila British Journal of Pharmacology (2007) 152, 1325; doi:10.1038/sj.bjp.0707613 [source] Endomorphin analogues containing D -Pro2 discriminate different ,-opioid receptor mediated antinociception in miceBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2002Shinobu Sakurada The antagonistic actions of D -Pro2 -endomorphins on inhibition of the paw withdrawal response by endomorphins were studied in mice. D -Pro2 -endomorphin-1 and D -Pro2 -endomorphin-2, injected intrathecally (i.t.), had no significant effect on the nociceptive thermal threshold alone. When D -Pro2 -endomorphin-1 (0.05,0.1 pmol) was injected simultaneously with i.t. endomorphin-1 (5.0 nmol) or endomorphin-2 (5.0 nmol), antinociception induced by endomoprhin-1 was reduced significantly, whereas endomorphin-2-induced antinociception was not affected by D -Pro2 -endomorphin-1. Antinociception induced by i.t. endomorphin-2 (5.0 nmol) was reduced significantly by its analogue, D -Pro2 -endomorphin-2 (100 pmol), but not by D -Pro2 -endomorphin-1. D -Pro2 -endomorphin-1. D -Pro2 -endomorphin-1 also antagonized the antinociceptive effect of i.t. DAMGO, a ,-opioid receptor agonist, whereas D -Pro2 -endomorphin-2 failed to reduce the effect of DAMGO. These results suggest that endomorphin analogues containing D -Pro2 are able to discriminate the antinociceptive actions of ,1 - and ,2 -opioid receptor agonists at the spinal cord level. British Journal of Pharmacology (2002) 137, 1143,1146. doi:10.1038/sj.bjp.0705047 [source] The clinical use of buprenorphine in opiate addiction: evidence and practiceACTA NEUROPSYCHIATRICA, Issue 5 2004Fergus D. Law Buprenorphine is a partial ,-opioid receptor agonist that is being increasingly used in clinical practice in the treatment of opioid dependence in the UK, USA, and, elsewhere. Its unique pharmacological properties mean it is a relatively safe drug, it can be given by alternate day dispensing, and it is associated with relatively mild symptoms on withdrawal. The interpretation of the research literature on buprenorphine is however, complex, and often appears to be in conflict with how buprenorphine is used in clinical practice. This article describes these apparent contradictions, their likely explanations, and how these may further inform our clinical practice. The article also describes the clinically relevant pharmacological properties of buprenorphine, compares it to methadone, relates the evidence to clinical experience, and provides practical advice on how to manage the most common clinical techniques. The best quality evidence suggests that very rapid buprenorphine induction is not associated with a higher drop-out rate than methadone, that buprenorphine is probably as good as methadone for maintenance treatment, and is superior to methadone and ,-2 adrenergic agonists for detoxification. However, buprenorphine cannot yet be considered the ,gold standard' treatment for opiate dependence because of the higher drop-out rates that may occur on induction using current techniques, its high-cost relative to methadone, and because the place of buprenorphine in treatment is still continuing to evolve. [source] The potential for ,-opioid receptor agonists to be anti-emetic in humans: a review of clinical dataACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010KEVIN D. JOHNSTON In animal models of vomiting, ,-opioid (MOP, OP3) receptors mediate both emesis and anti-emesis. ,-receptors within the blood,brain barrier, mediating anti-emesis, are more rapidly accessible to lipid-soluble ,-opioid receptor agonists such as fentanyl than to morphine, and fentanyl has broad-spectrum anti-emetic effects in a number of species. Whether a similar situation exists in humans is not known. A search was performed for clinical studies comparing the emetic side effects of opioids administered peri-operatively in an attempt to identify differences between morphine and more lipid-soluble ,-receptor-selective agonists such as fentanyl. Overall, the evidence appears to suggest that fentanyl and other phenylpiperidines are associated with less nausea and vomiting than morphine, but not all studies support this, and fentanyl-like drugs are associated with nausea and vomiting per se. Good evidence, however, exists to show that fentanyl and alfentanil do not cause more nausea and vomiting than the ultra fast-acting remifentanil. Because remifentanil is cleared rapidly post-operatively, such trials suggest that the emetic side effects of fentanyl and alfentanil are minimal. The clinical evidence, although limited, is at least consistent with the possibility that central ,-opioid receptors may mediate anti-emesis in humans. It is possible that the role of ,-opioid agonists in anti-emesis may become clearer in the future as a result of the use of peripheral ,-opioid receptor antagonists. [source] Recent advances in selective opioid receptor agonists and antagonistsMEDICINAL RESEARCH REVIEWS, Issue 2 2004Masakatsu Eguchi Abstract Opioid analgesics provide outstanding benefits for relief of severe pain. The mechanisms of the analgesia accompanied with some side effects have been investigated by many scientists to shed light on the complex biological processes at the molecular level. New opioid drugs and therapies with more desirable properties can be developed on the bases of accurate insight of the opioid ligand,receptor interaction and clear knowledge of the pharmacological behavior of opioid receptors and the associated proteins. Toward this goal, recent advances in selective opioid receptor agonists and antagonists including opioid ligand,receptor interactions are summarized in this review article. © 2003 Wiley Periodicals, Inc. Med Res Rev, 24, No. 2, 182,212, 2004 [source] Gender differences in drug effects: implications for anesthesiologistsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2003H. Pleym Background:, The gender aspect in pharmacokinetics and pharmacodynamics of anesthetics has attracted little attention. Knowledge of previous work is required to decide if gender-based differences in clinical practice is justified, and to determine the need for research. Methods:, Basis for this paper was obtained by Medline searches using the key words ,human' and ,gender' or ,sex,' combined with individual drug names. The reference lists of these papers were further checked for other relevant studies. Results:, Females have 20,30% greater sensitivity to the muscle relaxant effects of vecuronium, pancuronium and rocuronium. When rapid onset of or short duration of action is very important, gender-modified dosing may be considered. Males are more sensitive than females to propofol. It may therefore be necessary to decrease the propofol dose by 30,40% in males compared with females in order to achieve similar recovery times. Females are more sensitive than males to opioid receptor agonists, as shown for morphine as well as for a number of kappa (OP2) receptor agonists. On this basis, males will be expected to require 30,40% higher doses of opioid analgesics than females to achieve similar pain relief. On the other hand, females may experience respiratory depression and other adverse effects more easily if they are given the same doses as males. Conclusion:, These examples illustrate that gender should be taken into account as a factor that may be predictive for the dosage of several anesthetic drugs. Moreover, there is an obvious need for more research in this area in order to further optimize drug treatment in anesthesia. [source] Endomorphin analogues containing D -Pro2 discriminate different ,-opioid receptor mediated antinociception in miceBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2002Shinobu Sakurada The antagonistic actions of D -Pro2 -endomorphins on inhibition of the paw withdrawal response by endomorphins were studied in mice. D -Pro2 -endomorphin-1 and D -Pro2 -endomorphin-2, injected intrathecally (i.t.), had no significant effect on the nociceptive thermal threshold alone. When D -Pro2 -endomorphin-1 (0.05,0.1 pmol) was injected simultaneously with i.t. endomorphin-1 (5.0 nmol) or endomorphin-2 (5.0 nmol), antinociception induced by endomoprhin-1 was reduced significantly, whereas endomorphin-2-induced antinociception was not affected by D -Pro2 -endomorphin-1. Antinociception induced by i.t. endomorphin-2 (5.0 nmol) was reduced significantly by its analogue, D -Pro2 -endomorphin-2 (100 pmol), but not by D -Pro2 -endomorphin-1. D -Pro2 -endomorphin-1. D -Pro2 -endomorphin-1 also antagonized the antinociceptive effect of i.t. DAMGO, a ,-opioid receptor agonist, whereas D -Pro2 -endomorphin-2 failed to reduce the effect of DAMGO. These results suggest that endomorphin analogues containing D -Pro2 are able to discriminate the antinociceptive actions of ,1 - and ,2 -opioid receptor agonists at the spinal cord level. British Journal of Pharmacology (2002) 137, 1143,1146. doi:10.1038/sj.bjp.0705047 [source] | |||||||||||||