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)

Antinociceptive activity of seven pentapeptide fragments of human adenovirus type 2 (Ad2) virion proteins: Thr-Val-Pro-Pro-Arg (1), Thr-Arg-Pro-Pro-Arg (2), Thr-Gly-Pro-Pro-Thr (3), Pro-Arg-Pro-Pro-Thr (4), Phe-Val-Pro-Pro-Arg (5), Ala-Arg-Pro-Pro-Ala (6), Tyr-Gly-Pro-Pro-Lys (7)--analogs of known tuftsin inhibitor Thr-Lys-Pro-Pro-Arg, was measured by hot-plate procedure. Also two tuftsin-like fragments of epitopes of HIV-1 and HIV-2: Thr-Lys-Ala-Lys (8), Thr-Lys-Glu-Lys (9), and tuftsin analog Thr-Lys-Asp-Lys (10) were tested. In the control experiments the effects of tuftsin and pentapeptide tuftsin inhibitor were also studied. The peptides 2, 4 and 5 were found to produce very strong analgesia after the icv injection. It was observed that pretreatment with peptide 8 remarkably diminished the antinociceptive effect induced by tuftsin.
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PMID:The analgesic activity of some tuftsin- and tuftsin inhibitor-like fragments of the viral coat proteins. 822 Jun 60

Based on pharmacological evidence that inhibitory amino acids mediate vaginocervical mechano-stimulation produced analgesia (VSPA), we hypothesized that inhibitory amino acids would be released endogenously in the spinal cord in response to vaginocervical mechano-stimulation (VS). This hypothesis was tested by HPLC analysis of the amino acid content of 5-min superfusates of the spinal cord before, during and after VS (400 g force applied against the cervix) in urethane-anesthetized rats. Utilizing an in vivo push-pull superfusion method, artificial cerebrospinal fluid was continuously superfused over the spinal cord through the intrathecal space surrounding the sacral-lower thoracic region. In addition, concentrations of amino acids in the superfusate were measured in response to KCl stimulation (increasing the superfusion medium from 3.4 to 40.0 mM KCl to produce non-specific depolarization), and noxious hind paw mechano-stimulation (pinching the hind paw to produce a sustained flexor response in ipsilateral hind leg). There was a significant increase in the concentration of Gly, Tau, Asp, Glu and Lys in the superfusate in response to VS (n = 8) and to KCl (n = 8), but not to hind paw stimulation (n = 5). Also, GABA concentrations increased in response to KCl, and the concentration of Ala, Ser, Gln, Thr, Arg and Phe increased in response to VS, however, GABA levels were sometimes below the limits of detection. In contrast, there was no significant change in any amino acid concentration in response to hind paw pinch stimulation, and VS did not significantly affect the concentrations of Tyr, His, Ile, Leu, Met, Trp or Val. The present findings support our hypothesis that VS releases inhibitory amino acids in the spinal cord. Moreover, other amino acids, including 'excitatory' amino acids, are released into the superfusate. The profile of amino acid release in response to VS differs from that in response to paw pinch or KCl administration.
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PMID:Release of amino acids into regional superfusates of the spinal cord by mechano-stimulation of the reproductive tract. 824 40

The aim of this study was to compare the analgesic efficacy of intravenous lysine acetylsalicylate 1.8 g, indomethacin 100 mg and pethidine 100 mg in acute renal colic in a randomized double-blind clinical trial. One hundred and fifty patients with acute renal colic were divided into three groups. The first group received lysine acetylsalicylate 1.8 g, the second group received indomethacin 100 mg and the third group received pethidine 100 mg. The degree of pain relief was recorded 5, 15, 30 and 60 min after intravenous administration of the drugs. There was no statistically significant difference between the degree of analgesia provided by pethidine and indomethacin. Lysine acetylsalicylate was less effective than indomethacin and pethidine. It is concluded that intravenous indomethacin is an effective alternative to intravenous pethidine in the treatment of acute renal colic. Intravenous lysine acetylsalicylate is inferior to intravenous indomethacin in treatment of acute renal colic.
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PMID:Comparative study of the efficacy of lysine acetylsalicylate, indomethacin and pethidine in acute renal colic. 902 98

Nonsteroidal antiinflammatory drugs act largely peripherally by blocking the local synthesis of prostaglandins. The aim of this study was to evaluate whether the addition of a small dose of lysine acetylsalicylate (LA) to the prilocaine used for intravenous regional anesthesia (IVRA) would improve the quality of postoperative analgesia. Sixty patients undergoing lower extremity IVRA for foot or ankle surgery were randomly assigned to three double-blind groups: LA-IVRA where 90 mg of LA was mixed with prilocaine 0.5% for IVRA and 1 mL of 0.9% NaCl administered intravenously (IV) through the forearm catheter after tourniquet inflation; LA-IV where 1 mL of 0.9% NaCl was mixed with prilocaine and 90 mg of LA administered IV; and placebo where 1 mL of 0.9% NaCl was administered both with prilocaine for the IVRA and IV. Duration of analgesia (time elapsed between tourniquet release and first injection of morphine, expressed as mean +/- SD) was significantly longer (P < 0.05) in LA-IVRA (387 +/- 216 min) when compared with LA-IV (175 +/- 264 min) and placebo (126 +/- 201 min). Analgesic requirements remained significantly lower in LA-IVRA when compared with placebo only during the first six postoperative hours, LA-IV being in an intermediate position. Pain scores were significantly lower in LA-IVRA during the first postoperative hour when compared with LA-IV and during the first 3 postoperative hours when compared with placebo. We conclude that 90 mg of LA (corresponding to 50 mg of acetylsalicylic acid) added to prilocaine 0.5% during IVRA improves the quality of postoperative analgesia in the early postoperative period.
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PMID:Effect on postoperative analgesia of small-dose lysine acetylsalicylate added to prilocaine during intravenous regional anesthesia. 914 35

The tridecapeptide, neurotensin elicits naloxone-insensitive analgesia after its intracebroventricular administration in mice. We used this central pharmacological effect to assess the putative contribution of the endopeptidase 3.4.24.15 to central inactivation of the peptide. By means of combinatorial chemistry, we previously designed the first potent endopeptidase 3.4.24.15 inhibitor. This agent, Z-(L,D)Phe psi(PO2CH2)(L,D)Ala-Lys-Met (phosphodiepryl 21), is shown here to behave as a fully specific endopeptidase 3.4.24.15 inhibitor, as demonstrated by the absence of effect on a series of other exo- and endopeptidases belonging to various classes of proteolytic activities present in murine brain membranes. Furthermore, central administration of phosphodiepryl 21 drastically prolongs the forepaw licking latency of mice tested on the hot plate and injected with sub-maximally active doses of neurotensin. Altogether, our results demonstrated that, in addition to endopeptidase 3.4.24.16, endopeptidase 3.4.24.15 likely contributes to the physiological termination of the neurotensinergic message in murine brain.
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PMID:Contribution of endopeptidase 3.4.24.15 to central neurotensin inactivation. 934 27

Several lines of evidence have shown that neurotensin can modulate dopamine neurotransmission. It has been suggested that neurotensin has potential antipsychotic activity because it reduces dopaminergic activity preferentially in the nucleus accumbens. In the present study, the effects of neurotensin and NT1 (N alpha Me-Arg-Lys-Pro-Trp-TIe-Leu or Eisai hexapeptide), a metabolically stable and systemically active neurotensin agonist, were examined in several models of antipsychotic activity and side effect liability in mice; analgesic and hypothermic effects of both compounds also were determined. Up to high doses, neurotensin (5.0 and 10.0 micrograms, i.c.v.) and NT1 (10.0 and 20.0 mg/kg, i.p.) did not produce catalepsy. A much lower dose of neurotensin (0.03 microgram, i.c.v.) significantly reduced amphetamine- and phencyclidine-stimulated locomotor activity; NT1 also diminished amphetamine- and phencyclidine-stimulated locomotion with ED50 values of 0.3 and 0.4 mg/kg, i.p., respectively. Neurotensin (0.01-0.3 microgram, i.c.v.) and NT1 (0.1-1.0 mg/kg, s.c.) also produced dose-dependent analgesia in the paw pressure test and decreased body temperature; these effects were insensitive to pretreatment with naloxone (10.0 mg/kg, i.p.). Together, the results support the hypothesis that neurotensin agonists have antipsychotic and analgesic activity. Moreover, the data suggest that such compounds may not produce extrapyramidal side effects.
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PMID:Comparative antipsychotic profiles of neurotensin and a related systemically active peptide agonist. 939 65

The purpose of this prospective cohort study was to compare metabolic effects of epidural or patient controlled analgesia (PCA) in patients undergoing major upper abdominal surgery. Seventeen patients undergoing major upper abdominal surgery were included: 10 received perioperative epidural analgesia (Group I) and the remainder received morphine via a PCA device for postoperative analgesia (Group II). A number of measures compared between one day preoperatively (day 1) and day 2 postoperatively included femoral arterial and venous blood concentrations of glucose, lactate, pyruvate and amino acids. In addition, the relevant flux values were measured from the products of the respective arteriovenous substrate concentration differences and calf blood flow. The efflux of lactate from peripheral tissues was greater in Group II than in Group I (P < 0.01): glucose and pyruvate efflux did not differ between groups. There was no difference between groups in mean individual and total flux of amino acids on day-1. However increased efflux between day-1 and day 2 was found for alanine, valine, isoleucine, leucine, phenylalanine, lysine, arginine in both groups, and for serine, glycine, tyrosine and histidine in Group II (P < 0.05). The efflux of glycine, methionine, amino benzoic acid, alanine, and lysine was less in Group I than Group II on day 2 (P < 0.05). There was a significant difference in the total amino acid flux on day 2 (Group I = -1.2 mumol. (100 ml tissue)-1.min-1 cf Group II = -2.5 mumol. (100 ml tissue)-1.min-1; P = 0.04). In conclusion, perioperative epidural analgesia was associated with a reduced postoperative amino acid efflux two days following major upper abdominal surgery.
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PMID:Epidural analgesia reduces the release of amino acids from peripheral tissues in the ebb phase of the metabolic response to major upper abdominal surgery. 1005 Feb 19

We identified a novel neuropeptide and named it "nocistatin." Its presence was expected by analysis of the precursor for the neuropeptide nociceptin or orphanin FQ (Noc/OFQ), previously identified as an endogenous ligand for the orphan opioid receptor-like receptor. The precursor prepronociceptin/orphanin FQ (ppNoc/OFQ) comprises at least two bioactive peptides, nocistatin and Noc/OFQ. Noc/OFQ is involved in a broad range of pharmacological actions in various tissues from the central nervous system to the periphery. In pain transmission, Noc/OFQ is reported to have different effects including nociception, no effect, and analgesia, depending on the animal species tested, doses, route of administration, and so on. We found that intrathecal administration of Noc/OFQ induced pain responses including allodynia and hyperalgesia. Simultaneous administration of nocistatin blocked the allodynia and hyperalgesia induced by Noc/OFQ, whereas anti-nocistatin antibody decreased the threshold for the Noc/OFQ-induced allodynia. The endogenous heptadecapeptide nocistatin was isolated from bovine brains and recently identified in mouse, rat, and human brain and in human cerebrospinal fluid. Although human, rat and mouse ppNoc/OFQ produced larger respective counterparts with 30, 35, and 41 amino acid residues, all peptides showed the antinociceptive activity. This activity was ascribed to the carboxyl-terminal hexapeptide of nocistatin, Glu-Gln-Lys-Gln-Leu-Gln, which is conserved beyond species. Nocistatin also attenuated the allodynia and hyperalgesia evoked by prostaglandin E(2) and the inflammatory hyperalgesia induced by formalin or carrageenan/kaolin, and reversed the Noc/OFQ-induced inhibition of morphine analgesia at picogram doses. Furthermore, nocistatin counteracted the impairment of learning and memory induced by Noc/OFQ or scopolamine. Nocistatin is widely present in the spinal cord and brain. Although nocistatin did not bind to the Noc/OFQ receptor, it bound to the membrane of mouse brain and spinal cord with a high affinity. Nocistatin is a novel bioactive peptide produced from the same precursor as Noc/OFQ, and it plays important roles in the regulation of pain transmission and learning and memory processes in the central nervous system.
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PMID:Nocistatin: a novel neuropeptide encoded by the gene for the nociceptin/orphanin FQ precursor. 1099 44

The tetrapeptide DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) is a polar and selective mu agonist showing poor penetration of the placental and blood-brain barriers. In an effort to enhance the potency of DALDA, analogues containing 2',6'-dimethyltyrosine (Dmt), N,2',6'-trimethyltyrosine (Tmt), 2'-methyltyrosine (Mmt) or 2'-hydroxy,6'-methyltyrosine (Hmt) in place of Tyr1, or Orn or alpha,gamma-diaminobutyric acid (A2bu) in place of Lys4, were synthesized. All compounds displayed high mu receptor selectivity in the rat and guinea pig brain membrane binding assays and most of them were more potent mu agonists than DALDA in the mu receptor-representative guinea pig ileum assay, with [Dmt1]DALDA showing the highest potency. Because of its extraordinary mu agonist potency, high mu selectivity, polar character (charge of 3 + ) and metabolic stability, [Dmt1]DALDA has potential for use in obstetrical or peripheral analgesia.
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PMID:Synthesis and in vitro opioid activity profiles of DALDA analogues. 1112 15

DALDA (H-Tyr-D-Arg-Phe-Lys-NH(2)) and [Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH(2)) (Dmt = 2',6'-dimethyltyrosine) are potent and highly selective mu-opioid agonists (K(i)(delta)/K(i)(mu) > 10,000 and K(i)(kappa)/K(i)(mu) > 100). Both peptides carry a 3+ charge at physiological pH. Their antinociceptive and respiratory effects were compared with morphine (MOR) after intrathecal administration in rats. Both DALDA and [Dmt1]DALDA produced dose-dependent and naloxone-reversible antinociceptive effects with relative potencies of 14 and 3000x that of MOR. The antinociceptive potency of [Dmt1]DALDA far exceeded its affinity and potency at the mu-opioid receptor and may be explained by its ability to inhibit norepinephrine (NE) uptake in spinal cord synaptosomes. The antinociceptive response to [Dmt1]DALDA was significantly attenuated by the alpha(2)-adrenergic antagonist yohimbine. Thus, [Dmt1]DALDA may be regarded as a drug with dual actions, and its antinociceptive potency is better described by both its affinity and potency at mu-opioid receptors, and its potency at inhibiting NE uptake. The analgesic duration of an equipotent dose of MOR, DALDA, and [Dmt1]DALDA was 3, 7, and 13 h, respectively, and the long duration may be due to the hydrophilic nature of these peptide analogs. Respiratory effects were determined using whole body plethysmography at 3 and 30x the antinociceptive ED(50). A significant depression in minute ventilation was observed with the higher dose of morphine and both doses of DALDA, but not with either dose of [Dmt1]DALDA. Because of its high antinociceptive potency, long duration of action, and low propensity to induce respiratory depression, [Dmt1]DALDA is of interest as a drug candidate for intrathecal analgesia.
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PMID:Antinociceptive and respiratory effects of intrathecal H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA) and [Dmt1] DALDA. 1125 64


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