Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mu opioid receptor ligand [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAGO) and delta opioid receptor ligand [D-Pen2,D-Pen5]enkephalin (DPDPE) show similar specificity in competition binding studies in whole brain homogenate in rat and mouse. However, in saturation studies, the density and affinity of DPDPE binding sites were substantially greater in the mouse. There was no difference between the mouse and rat in the density and affinity of DAGO sites. Results from dose-response studies for analgesia using the same ligands administered i.c.v. in both species paralleled the binding studies. DAGO was approximately 2 times more potent in the mouse compared to the rat; while DPDPE was more than 15 times more potent in the mouse. Thus, binding capacity and affinity differences appear to be related to the functional potency of the mu and delta ligands in the two species. These results suggest that the difference in potency of DPDPE between rat and mouse is related to the differences in brain delta opioid receptors.
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PMID:Species differences in mu- and delta-opioid receptors. 164 25

Ohmefentanyl has been shown to be 6300 times more potent than morphine for analgesia. The receptor binding characteristics and distribution of [3H]ohmefentanyl in rat brain sections are presented. [3H]Ohmefentanyl bound with high affinity to opioid receptors in a saturable manner (Kd = 0.95 +/- 0.08 nM, Bmax = 337 +/- 14 fmol/mg protein). We used various currently available specific mu, delta and kappa ligands to show that [3H]ohmefentanyl has a high selectivity for the mu opioid receptor. However, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) was unable to completely inhibit [3H]ohmefentanyl specific binding, while complete inhibition was observed with fentanyl derivatives and the benzomorphan derivative, ethylketocyclazocine. This remaining 20% DAGO-inaccessible [3H]ohmefentanyl specific binding did not correspond to either mu1, delta or kappa sites. Haloperidol and 1,3-di-o-tolylguanidine were able to inhibit DAGO-inaccessible [3H]ohmefentanyl specific binding, suggesting that [3H]ohmefentanyl might also bind to haloperidol-sensitive sigma sites. The topographical distribution of [3H]ohmefentanyl found by autoradiography was generally similar to that of [3H]DAGO. However, in agreement with the biochemical results, quantitative analysis revealed additional sites in several rat brain regions, the greatest discrepancies with [3H]DAGO distribution being observed in cerebellum, central grey, hippocampal formation and locus coeruleus. Finally, our results suggest that this capacity of binding to both mu and sigma sites is shared by various fentanyl derivatives.
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PMID:[3H]ohmefentanyl preferentially binds to mu-opioid receptors but also labels sigma-sites in rat brain sections. 164 20

The relationship between analgesic activity, measured as the hot plate reaction time, and respiratory depression, measured as ventilatory frequency, was investigated in mice for a variety of mu opioid receptor agonists with differing selectivities for mu receptors compared with delta receptors. There was a weak correlation between analgesia and respiratory depression for opioids with the greatest selectivity for mu opioid receptors compared with delta receptors, such as alfentanil. The strength of the correlation increased for opioids which had greater delta receptor activity, such as morphine and fentanyl. Etorphine, which has almost equal affinity for mu, delta and, incidentally, kappa receptors, showed a strong correlation between analgesia and respiratory depression. We conclude that the predictability of the degree of respiratory depression produced by a given analgesic dose of an opioid appears to decrease with its selectivity for mu opioid receptors, at least in the mouse.
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PMID:Relationship between analgesia and respiratory depression for mu opioid receptor agonists in mice. 168 79

This paper describes the synthesis and kappa and mu opioid receptor binding affinity of some conformationally restrained derivatives of the arylacetamide group in the selective kappa opioid receptor agonist (+/-)-trans-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]benzo [b]thiophene-4-acetamide monohydrochloride (1,PD117302), which is an analogue of U-50, 488. The methyl-substituted derivatives (+/-)-trans-N, alpha-dimethyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzo-[b] thiophene-4-acetamide monohydrochloride (6a,b) possess significantly weaker affinity than 1 for the kappa opioid receptor (Ki = 172 and 3.7 nM, respectively). It is proposed that this is due to the conformational restriction imposed by the methyl group of 6. In order to test this proposal the acenaphthene derivative and the 4,5-dihydro-3H-naphtho [1,8-bc]thiophene derivative were prepared. The acenaphthene derivative (+)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro [4.5]dec-8-yl]acenaphthenecarboxamide monohydrochloride (9) was found to have high kappa opioid receptor affinity and selectivity (kappa Ki = 0.37 +/- 0.05 nM, mu/kappa = 659, delta/kappa = 1562) and is 100 times more potent than morphine as an analgesic in the rat paw pressure test for analgesia after intravenous administration (MPE50 = 0.014 and 1.4 mg/kg, respectively). The 4,5-dihydro-3H-naphtho[1,8-bc]thiophene derivative (-)-4,5-dihydro-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro [4.5]dec-8-yl]-3H-naphthol[1,8-bc]thiophene-5-carboxamide p-toluenesulfonate (17) also has high kappa opioid receptor affinity and selectivity (kappa Ki = 4.65 nM, mu/kappa = 109).
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PMID:Highly selective kappa opioid analgesics. 4. Synthesis of some conformationally restricted naphthalene derivatives with high receptor affinity and selectivity. 184 19

Equipotent antinociceptive doses, as determined by a tail-flick response, for centrally administered (periaqueductal gray) morphine (M) and D-Ala2, D-Leu5 enkephalin (DADLE) were established as 5 micrograms and 19 micrograms, respectively. Chronic (28 day) subcutaneous infusion of clomipramine (CMI) via an Alzet minipump attenuated both central M-and DADLE-induced analgesia by day 15; attenuation persisted for the duration of the infusion (day 29). Within 7 days following removal of the pump, antinociceptive responses to M and DADLE returned to near pre-CMI levels. Our results indicate a similarity between M and DADLE with regard to attenuation of their antinociceptive action by chronic CMI. This attenuation may be due to decreased mu opioid receptor sensitivity or density resulting from chronic tricyclic antidepressant administration.
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PMID:Effects of chronic clomipramine on central DADLE antinociception. 225 Sep 23

The pharmacological effects of morphine, namely analgesic, hyperthermic and cataleptic effects, were assessed in rats rendered tolerant to U-50,488H, a kappa opioid receptor agonist. Male Sprague-Dawley rats were injected intraperitoneally with U-50,488H (25 mg/kg) twice a day for four days. The rats which served as controls were injected similarly with the vehicle. Chronic administration of U-50,488H resulted in the development of tolerance to its analgesic and hypothermic effects, but not to its diuretic effect. The development of tolerance to the pharmacological effects of U-50,488H was associated with decreased binding of [3H]ethylketocyclazocine [( 3H]EKC) to brain and spinal cord membranes. The decreased binding of [3H]EKC in U-50,488H-treated rats was due to changes in the Bmax value; the Kd values remained unaltered. Intraperitoneal administration of morphine (8 mg/kg) to rats produced analgesia (as determined by the tail-flick test) and hyperthermia. A dose of 50 mg/kg of morphine produced cataleptic response. The intensity of analgesic, hyperthermic and cataleptic effects of morphine were unaltered in rats tolerant to U-50,488H. The development of tolerance to analgesic and hypothermic effects of U-50,488H were associated with down-regulation of brain and spinal cord kappa opioid receptors. Finally, U-50,488H does not confer cross-tolerance to morphine, a predominantly mu opioid receptor agonist.
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PMID:Effects of morphine in rats treated chronically with U-50,488 H, a kappa opioid receptor agonist. 254 58

The role of mu and delta opioid receptors in the spinal and supraspinal analgesic actions of morphine and [D-Pen2, L-Pen5] enkephalin were examined in the tail-flick test utilizing the mu opioid receptor deficient CXBK mouse and BALB/cBy and C57BL/6By, the progenitor strains of CXBK. The analgesic effects of i.c.v. administered morphine were equivalent in the CRS-CD1 (Swiss) standard laboratory mice and the progenitor strains of CXBK. Morphine did not, however, produce analgesia in the CXBK mice at doses greater than 10 times the ED50 dose in the progenitor strains. Similarly, the analgesic effect of i.c.v. [D-Ala2, NMePhe4, Gly-ol]enkephalin, a highly selective mu receptor peptide agonist, also was reduced greatly in the CXBK mice. These data are consistent with the deficiency in mu opioid receptors observed autoradiographically in this strain. In contrast, the highly selective delta opioid receptor peptide agonist [D-Pen2, L-Pen5]enkephalin was equipotent i.c.v. in the CXBK mice and in the progenitor strains of CXBK. In contrast to the effects produced by i.c.v. administration, the analgesic effects of intrathecally administered morphine were similar between CRS-CD1 and CXBX strains of mice. These results suggest that 1) both mu and delta opioid receptors can mediate supraspinal analgesia and 2) that the receptor(s) involved in spinally mediated analgesia is (are) quite distinct from those involved supraspinally.
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PMID:Examination of the involvement of supraspinal and spinal mu and delta opioid receptors in analgesia using the mu receptor deficient CXBK mouse. 283 33

The effects of beta-FNA, a highly selective and irreversible mu opioid receptor antagonist, in altering body and brain development in preweaning rats were determined. Animals given beta-FNA did not differ from controls in body weights, brain and cerebellar weights, macroscopic dimensions of the brain, the area of the cerebellum, or in organ weight. The dosage of beta-FNA utilized (5 mg/kg) blocked morphine-induced analgesia (2 mg/kg morphine sulfate, SC) for each injection period (i.e., 48 hr). In contrast to beta-FNA treatment, rats given naltrexone (50 mg/kg SC) in a regimen which completely blocked the opioid receptor throughout ontogeny exhibited marked increases in somatic and neurobiological growth. These results suggest that, in and by themselves, mu receptors selectively antagonized by beta-FNA do not play an important role in regulating development.
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PMID:beta-Funaltrexamine (beta-FNA) and the regulation of body and brain development in rats. 301 87

Jimpy (B6CBA-A W-J/A-Ta jp) mice, which are known to be deficient in neuronal cerebroside sulfate (a putative component of the mu opioid receptor), were non-responsive in the tail flick test (compared to littermate controls and a standard Swiss strain of mouse) to analgesic doses of two mu opioid receptor agonists, morphine sulfate and [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO). However, the jimpy mice responded normally (compared to controls) to the analgesic effects of the selective delta opioid receptor agonist [D-Pen2,L-Pen5]enkephalin (DPLPE). These results suggest (1) that delta opioid receptors can mediate analgesia and (2) that cerebroside sulfate is not necessary for delta opioid receptor activation.
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PMID:[D-Pen2,L-Pen5]enkephalin induced analgesia in the jimpy mouse: in vivo evidence for delta-receptor mediated analgesia. 303 73

The effects of beta-FNA, a highly selective and irreversible mu opioid receptor antagonist, in altering tumor response in A/Jax mice inoculated with S20Y cells were determined. Inoculation of neuroblastoma cells in control subjects resulted in 100% tumor incidence within 16 days, and mean and median survival times of 36 and 35 days, respectively, following tumor inoculation. Tumor incidence and survival times were comparable to controls for mice given chronic injections of 2 mg/kg and 10 mg/kg beta-FNA every 48 h beginning 2 days after tumor inoculation. Tumor growth was subnormal in the 10 mg/kg beta-FNA group. Both dosages of beta-FNA were found to block morphine-induced analgesia for 48 h. These results suggest that, in and by themselves, mu receptors selectively antagonized by beta-FNA do not play an important role in neuro-oncogenic events.
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PMID:beta-Funaltrexamine (beta-FNA) and neural tumor response in mice. 405 12


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