Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of the selective mu-ligand [D-Ala2, MePhe4, Glyol5]enkephalin (DAMGO) and the selective delta-ligand [D-Ser2, Leu5, Thr6]enkephalin (DSLET) with the binding sites in rat brain cortex membranes, has been studied. Analysis of the binding isotherms in the presence and absence of nonlabelled DAMGO and DSLET revealed that these ligands can interact with both superhigh affinity and high affinity binding sites that are distinct from one another. Prolonged administration of morphine and formation of physical dependence caused no appreciable changes in the parameters of either the superhigh affinity binding sites for the mu-ligands or the high affinity binding sites for mu- and delta-ligands. At the same time, the affinity of the superhigh affinity site for delta-ligands increased 3.5 times (tau 1/2 approximately equal to 17.5 h).
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PMID:[Heterogeneity of mu- and delta-opioid active sites in the mouse cerebral cortex. Selective increase in the affinity of a superhigh affinity delta-site during long-term administration of morphine]. 132 89

The use of the guinea pig ileum (GPI) and mouse vas deferens (MVD) to quantify opiate tolerance and physical dependence in the same preparation was examined. In the GPI, tolerance to and physical dependence on various opiates were induced by direct incubation with an agonist and tolerance and abstinence were assessed after its rapid removal by extensive washing. Dependence, as evidenced by an increase in twitch height and after removal of the agonist as compared to that before incubation, provided an index of the degree of physical dependence. The extent of the supersensitive response after agonist removal was noted to be related directly to the agonist concentration and the degree of tolerance development. Furthermore, the supersensitive response was found to be stereospecific, naloxone reversible and preferentially mu receptor-mediated. Likewise, tolerance to opiates could be demonstrated in the MVD by direct incubation with an agonist. Unlike the GPI, rapid removal of the agonist by washing did not produce a supersensitive response to electrical stimulation. However, a supersensitive response was demonstrable in the presence of naloxone. Thus, after a tolerant/dependent state was induced by incubation of the vas with a predetermined dose of [D-Ala2, D-Leu5]enkephalin that completely abolished the twitch response, the subsequent addition of naloxone resulted in a supersensitive response to electrical stimulation that was concentration-dependent. The maximum twitch response in the presence of naloxone, compared to that obtained before incubation with the agonist, provided an index of the extent of dependence.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Supersensitivity to electrical stimulation for assessing physical dependence on opioids in isolated tissues. 236 90

In light of more recent knowledge concerning endogenous opioid peptides and their multiple opiate receptors, we reevaluated the effects of morphine tolerance on opiate receptor binding parameters. Rats were implanted with morphine or placebo pellets, and [3H][D-Ala2,D-Leu5]enkephalin ([3H]DADL) was used to label brain membranes. Utilizing the technique of binding surface analysis, we observed a selective 47% up-regulation of lower affinity [3H]DADL binding sites (mu-noncompetitive delta binding sites) in morphine pelleted rats. To corroborate these results, we treated brain membranes with the site directed alkylating agent FIT (N-phenyl-N-[1-(2-p-isothiocyanato)phenyl-ethyl)-4-piperidinyl] propanamide), which results in membranes highly enriched with the lower affinity [3H]DADL binding site. Scatchard plots of [3H]DADL binding to FIT-treated membranes also revealed that chronic morphine treatment produced a 60-65% up-regulation of the mu-noncompetitive delta binding site. These data indicate that chronic morphine alters a selective subpopulation of opiate receptors that may play a role in the mechanisms of opiate tolerance and physical dependence.
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PMID:Morphine tolerance increases mu-noncompetitive delta binding sites. 301 57

The effect of D-Phenylalanine (D-Phe), putative carboxypeptidase A inhibitor and its four derivatives (T1-T4) on analgesia, development of tolerance and physical dependence to morphine, and on degradation of both exogenous and endogenous enkephalins was investigated. Systemic administration of either D-Phe or its derivatives produced naloxone-reversible analgesia in the hot-plate test in mice. Naloxone-precipitated morphine withdrawal syndrome was attenuated in mice after systemic subacute administration (7 days, 1.2 mmol/kg, sc) of D-phe derivatives, the development of tolerance to morphine being unchanged. In the presence of either D-Phe or its derivatives in incubation mixture (up to 10(-3) mol/l) the hydrolysis of exogenous 3H-Met5-and 3H-Leu5-enkephalin in striatal homogenates was slightly inhibited. Moreover, the addition of D-Phe or its derivatives seemed to increase the per cent of recovered endogenous Met5-enkephalin released from veratridine-depolarized striatal particles. In contrast, bestatin, an amino-peptidase inhibitor, and a mixture of dipeptides (Tyr-Tyr, Leu-Leu, Leu-Gly) markedly inhibited degradation of both endogenous and exogenous enkephalins in vitro. The results obtained in this study suggest that that pharmacological activity of D-Phe is not directly related to the endogenous opiate system.
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PMID:The effects of D-phenylalanine and its derivatives on enkephalin degradation in vitro: relation to analgesia and attenuation of the morphine withdrawal syndrome. 376 85

Previously, we have shown that the development of physical dependence on morphine in mice is inhibited substantially by treatment of mice with the highly selective, nonequilibrium delta-2 opioid receptor antagonist, naltrindole-5'-isothiocyanate. With the availability of the highly selective, nonequilibrium delta-1 opioid receptor antagonist, [D-Ala2,Leu5,Cys6]enkephalin, it was possible, in the present report, to examine the possible involvement of delta-1 opioid receptors in the development of opiate dependence. Mice were made physically dependent on morphine by s.c. implantation of morphine pellets (75-mg free base) for 3 days. The degree of dependence was quantified by determining the ED50 values of naloxone to precipitate withdrawal jumping and diarrhea. Neither sign of opiate withdrawal was affected by chronic treatment of animals with [D-Ala2,Leu5,Cys6]enkephalin during the morphine implant period. The data suggest that delta-1, as opposed to delta-2, opioid receptors are not involved in the development of physical dependence on morphine. This fact takes on added significance because the recently cloned delta opioid receptors appear to be the delta-2 subtype and the present data together with previous findings suggest that the cloned receptors may be proper models for the study of opiate dependence.
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PMID:Lack of involvement of delta-1 opioid receptors in the development of physical dependence on morphine in mice. 803 33

The dimeric enkephalin biphalin (Try-D-Ala-Gly-Phe-NH)2 was evaluated in mice using antinociceptive, gastrointestinal and physical dependence paradigms and compared with that of morphine (reference mu agonist) and etorphine (ultrapotent opioid agonist). Intracerebroventricular biphalin was 6.7- and 257-fold more potent than etorphine or morphine in eliciting antinociception. When administered i.t., biphalin produced only a 60% maximal antinociceptive effect in the tail-flick test even when given at doses up to 3 orders of magnitude higher than those effective i.c.v.; morphine was equipotent in this assay when given i.c.v. or i.t. Both morphine and biphalin were equipotent after i.p. administration. In spite of its antinociceptive effectiveness after i.p. administration. In spite of its antinociceptive effectiveness after i.p. administration, only a small fraction of [125I]biphalin was shown to penetrate to the brain (0.051 +/- 0.011%, at 20 min). After i.c.v. administration, biphalin antinociception was antagonized by receptor selective doses of beta-funaltrexamine (mu antagonist), naloxonazine (mu 1 antagonist), ICI 174,864 (delta antagonist) and [D-Ala2,Cys4]deltorphin (delta 2 antagonist), but not by [D-Ala2,Leu5,Cys6]enkephalin (delta 1 antagonist) or nor-binaltorphimine (kappa antagonist), whereas etorphine antinociception was significantly antagonized only by beta-funaltrexamine and naloxonazine. Intracerebroventricular biphalin inhibited gastrointestinal propulsion at doses 8-fold higher than those producing i.c.v. antinociception; i.c.v. morphine showed a similar antinociceptive and gastrointestinal propulsion A50. Intraperitoneal biphalin, but not i.p. morphine, showed little, if any, physical dependence, but both biphalin and morphine produced significant physical dependence when equiantinociceptive doses were infused i.c.v.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antinociceptive profile of biphalin, a dimeric enkephalin analog. 838 67