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 opioid activity pattern of 8 dermorphin tetrapeptides, W-Tyr-D-MetO-Phe-Xaa-Y (W = H, H2N-C = (NH); Xaa = Gly, 2-aminoethanol, sarcosine; Y = NH2, NH-alkyl), was determined in guinea-pig ileum (GPI) preparations and in brain binding assays and compared with their antinociceptive potency in mice. Almost all modifications increased potency on the GPI test as well as the antinociceptive action of the parent H-Tyr-D-Ala-Phe-Gly-NH2. Dermorphin, H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, and related tetrapeptide analogues show negligible K-binding activity and, like morphine, possess a higher affinity to mu- than delta-receptors. Nevertheless the correlation of analgesia with the effects on GPI and binding data separate the peptides from morphine. For example, in comparison with the opiate alkaloid H-Tyr-D-MetO-Phe-Gly-ol and H-Tyr-D-MetO-Phe-Gly-NH2 displayed a lower affinity for mu sites, a moderately higher potency on GPI but an exceptionally stronger analgesia, being respectively 350 and 1500 times as potent an analgesic as morphine. This may involve different subpopulations of opioid mu-receptors.
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PMID:Opioid peptides. Biological study of [D-MetO2] dermorphin analogues in relation to the plurality of opioid receptors. XI. 303 74

A 3-in-1 lumbar plexus block with the aid of a nerve stimulator was performed in 32 patients and a psoas compartment block was performed in five patients for muscle biopsy of the upper leg for diagnosis of malignant hyperthermia (MH) susceptibility. Twenty-two patients were found to be MH susceptible by the in vitro contracture test. Twenty patients received 40 ml prilocaine 1.5% with epinephrine 1:200,000 and two received 40 ml bupivacaine 0.5% with epinephrine 1:200,000 without any untoward reaction. The 3-in-1 block provides a high success rate and excellent analgesia for muscle biopsy of the upper leg. Amide local anaesthetics are safe in MH-susceptible patients.
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PMID:3-in-1 lumbar plexus block for muscle biopsy in malignant hyperthermia patients. Amide local anaesthetics may be used safely. 381 2

Amide local anaesthetics impair coagulation by inhibition of platelet function and enhanced fibrinolysis. The potential therefore exists that the presence of amide local anaesthetics in the epidural space could contribute to the therapeutic failure of an epidural autologous blood patch. Ropivacaine is an aminoamide local anaesthetic increasingly used for epidural analgesia and anaesthesia, particularly in obstetric practice. This study was undertaken to investigate whether concentrations of ropivacaine in blood, which could occur clinically in the epidural space, alter coagulation or fibrinolysis. Thromboelastography was used to assess clotting and fibrinolysis of blood to which ropivacaine had been added. Although modest alterations in maximum amplitude, coagulation time and alpha angle were observed, the effect of ropivacaine on clotting and fibrinolysis was not clinically significant. We conclude that it is unlikely that the presence of ropivacaine in the epidural space would reduce the efficacy of an early or prophylactic epidural blood patch.
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PMID:The effects of ropivacaine hydrochloride on coagulation and fibrinolysis. An assessment using thromboelastography. 1046 May 68

Amide local anaesthetics impair blood clotting in a concentration-dependent manner by inhibition of platelet function and enhanced fibrinolysis. We hypothesised that the presence of ropivacaine in the epidural space could decrease the efficacy of an epidural blood patch, as this technique requires that the injected blood can clot in order to be effective. Ropivacaine is an aminoamide local anaesthetic used increasingly for epidural analgesia during labour. The concentration of local anaesthetic in blood achieved in the epidural space during the performance of an epidural blood patch is likely to be the greatest which occurs (intentionally) in any clinical setting. This study was undertaken to investigate whether concentrations of ropivacaine in blood, which could occur: (i) clinically in the epidural space and (ii) in plasma during an epidural infusion of ropivacaine, alter platelet function. A platelet function analyser (Dade PFA-100, Miami) was employed to assess the effects of ropivacaine-treated blood on platelet function. The greater concentrations of ropivacaine studied (3.75 and 1.88 mg x ml(-1)), which correspond to those which could occur in the epidural space, produced significant inhibition of platelet aggregation. We conclude that the presence of ropivacaine in the epidural space may decrease the efficacy of an early or prophylactic epidural blood patch.
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PMID:The effects of ropivacaine hydrochloride on platelet function: an assessment using the platelet function analyser (PFA-100). 1146 42

Patients with bone cancer report severe pain and receive mu-opioids. We developed a family of peptidomimetic delta-agonists, one of which H2N-Tyr-dVal-Gly-Phe-Ala-OH ([dVal(L)2,Ala(L)5]E) binds with a 1700x affinity at the delta versus mu receptor. To examine the systemic analgesic efficacy of this delta-agonist versus morphine in osteosarcoma pain, osteosarcoma cells are injected into one femur of the anesthetized mouse. After 10-18 days, a decalcification of the injected femur occurs along with a pronounced tactile allodynia. IP morphine and [dVal(L)2,Ala(L)5]E produced a dose-dependent reversal of allodynia with the respective ED50 values being 5.3+/-1.9 mg/kg for morphine and 1.3+/-0.3 mg/kg for [dVal(L)2,Ala(L)5]E. Plotting peak effect versus area under the analgesic curve for doses of morphine and [dVal(L)2,Ala(L)5]E revealed overlapping curves suggesting that for a given effect, [dVal(L)2,Ala(L)5]E produced a similar duration of action as morphine. These effects were reversed by IP naloxone (3 mg/kg). IP naltrindole (1 mg/kg) preferentially reversed [dVal(L)2,Ala(L)5]E. The upper dose effects of morphine but not [dVal(L)2,Ala(L)5]E were limited by pronounced hyperactivity. No other effects were noted. These results show that IP [dVal(L)2,Ala(L)5]E through a delta receptor produces analgesia equal in efficacy to that of morphine but with a 4.5-fold greater potency. Over the doses examined, morphine actions were side effect limited. The delta side effects were not so limited, suggesting a favorable therapeutic ratio for delta-agonists in this pain model. These studies suggest that a systemically delivered delta-opioid agonist has pronounced analgesic properties on a preclinical cancer pain model.
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PMID:Cancer-related bone pain is attenuated by a systemically available delta-opioid receptor agonist. 1654 11

Prescription opioids abuse and associated deaths are an emerging concern in the USA. Vaccination against prescription opioids may provide an alternative to pharmacotherapy. An oxycodone hapten containing a tetraglycine linker at the C6 position (6OXY(Gly)(4)OH) conjugated to keyhole limpet hemocyanin (KLH) has shown early proof-of-efficacy in rodents as a candidate immunogen (6OXY(Gly)(4)-KLH) for the treatment of oxycodone abuse. In this study, oxycodone-based and hydrocodone-based haptens were conjugated to KLH to generate immunogens that would recognize both oxycodone and hydrocodone. Vaccination with 6OXY(Gly)(4)-KLH increased drug binding in serum, reduced drug distribution to brain, and blunted analgesia for both oxycodone and hydrocodone. An analogous C6-linked hydrocodone vaccine blocked hydrocodone effects but less so than 6OXY(Gly)(4)-KLH. C8-Linked hydrocodone immunogens had only limited efficacy. Amide conjugation showed higher haptenation ratios and greater efficacy than thioether conjugation to maleimide activated KLH (mKLH). The 6OXY(Gly)(4)-KLH vaccine may be used for treatment of prescription opioid abuse.
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PMID:Reduced antinociception of opioids in rats and mice by vaccination with immunogens containing oxycodone and hydrocodone haptens. 2324 38