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)

1. The effects of the substituted benzamide clebopride, an orthopramide, on nociception of chemical and thermal stimuli were investigated. 2. Clebopride (0.5, 1.0 and 2.0 mg/kg) promoted significant analgesia in the tail-flick and hot-plate tests and against abdominal constrictions produced by acetic acid or acetylcholine. 3. The analgesic effects of clebopride were not influenced by pretreatment with naltrexone (1-3 mg/kg). 4. The results suggest that clebopride induces analgesia against both thermal and chemical nociceptive stimuli, which is not mediated via opioid mechanisms.
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PMID:Antinociceptive effects of clebopride in the mouse. 755 55

The role of endogenous opioids in modulating pain transmission in amphibians was examined by two methods known to activate endogenous opioids in mammals. Analgesia was assessed using the acetic acid test in the Northern grass frog, Rana pipiens. One or 2 h of immobilization produced a significant analgesia lasting for at least 90 min. Systemic, but not spinal, administration of naloxone before immobilization prevented the analgesic effects seen in saline-pretreated controls. Spinal administration of the enkephalinase inhibitor, thiorphan, but not bestatin (both at 100 nmol/frog), produced significant analgesia. The analgesic effect of thiorphan was blocked by coadministration of intraspinal naloxone. These data are the first to suggest a role for endogenous opioid modulation of noxious stimuli in lower vertebrates by examination of stress-induced analgesia and the action of agents that inhibit enkephalin degradation.
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PMID:Analgesia produced by immobilization stress and an enkephalinase inhibitor in amphibians. 767 42

Opioid effects of 14 beta-(thioglycolamido)-7,8-dihydro-N(cyclopropylmethyl)- normorphinone (N-CPM-TAMO) were studied in the mouse tail-flick and acetic acid writhing assays. In the tail-flick test, N-CPM-TAMO failed to produce any antinociception after i.c.v. administration of up to 300 nmol. However, pretreatment of mice with N-CPM-TAMO produced a time- and dose-dependent antagonism of morphine-induced antinociception. The antagonism by N-CPM-TAMO lasted up to 48 hr, with a maximal effect at 24 hr after i.c.v. administration. Similarly, pretreatment of mice with N-CPM-TAMO at 24 hr also produced a dose-dependent antagonism of kappa-mediated antinociception, induced by U50,488 However, the antagonistic potency of N-CPM-TAMO against U50,488 was 100-fold less than against morphine. Pretreatment with N-CPM-TAMO had no effect on delta opioid receptor-mediated antinociception, as measured with [D-Pen2,D-Pen5]enkephalin. In the writhing assay, N-CPM-TAMO produced a time- and dose-dependent antinociception after i.c.v. administration, with a value of the dose producing 50% analgesia of 18.4 (10.6-31.9) nmol. The antinociceptive effect lasted up to 3 hr after administration. N-CPM-TAMO-induced antinociception was antagonized by coadministration of the kappa-selective antagonist, norbinaltorphimine. Pretreatment of mice with N-CPM-TAMO also produced a time- and dose-dependent antagonism of U50,488-induced antinociception, which lasted up to 72 hr, with a maximal effect at 24 hr after administration. These data indicate that N-CPM-TAMO is a mu-selective, long-term antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological study of 14 beta-(thioglycolamido)-7,8-dihydro-N(cyclopropylmethyl)-normor phinone (N-CPM-TAMO). 768 Jul 15

A series of 5-acyl-arylhydrazone 1-H pyrazolo [3,4-b] pyridine derivatives (1), planned by applying classical ring isosterism, were synthesized in order to evaluate the structure-activity relationship (SAR), especially the participation of the structural acyl-arylhydrazone subunit in the analgesia. The synthetic route used produced the derivatives 1 in approximately 40% overall yield, using 9 as key intermediate. The results obtained from this study showed that in general the compounds of this series present a powerful analgesic activity in the test of abdominal contortions induced by acetic acid i.p. in albino mice, indicating the participation of the acyl-arylhydrazone moiety, as well the relevance of the substituent of the aryl ring, in the activity.
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PMID:Synthesis and analgesic properties of 5-acyl-arylhydrazone 1-H pyrazolo [3,4-b] pyridine derivatives. 784 86

The involvement of a presynaptic autoinhibition of endogenous enkephalin release has been suggested as a possible explanation for the paradoxical analgesia induced by low doses of naloxone. This hypothesis was investigated by using the systemically active mixed inhibitor of enkephalin degrading enzymes, RB 101. As already described, in both hot plate (55 +/- 0.5 degrees C) and acetic acid (0.6%) abdominal constriction tests in mice, subcutaneous administration of naloxone produced biphasic effects, with antinociceptive responses at very low doses (microgram range) and hyperalgesia at higher dose (mg range). However at concentrations producing an extracellular increase in enkephalin levels and subsequent analgesia, the mixed inhibitor prodrug of the enkephalin-metabolizing enzymes RB 101 (20 or 100 mg/kg i.v. and 5 or 10 mg/kg i.v., in the hot plate test and in the abdominal constriction test, respectively) did not potentiate the paradoxical analgesia induced by naloxone. These results are inconsistent with a negative autoregulation of endogenous enkephalin release and could suggest the involvement of the diffuse noxious inhibitory controls (DNIC). Indeed, the finding that low doses of RB 101 (1 mg/kg i.v. in the hot plate test, and 250 micrograms/kg i.v. in the abdominal constriction test) were able to induce hyperalgesic responses could indicate that the DNIC are tonically activated by endogenous enkephalins accounting for the antinociceptive responses elicited by low doses of naloxone.
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PMID:Paradoxical analgesia induced by low doses of naloxone is not potentiated by complete inhibition of enkephalin degradation. 791 Mar 83

The analgesic and behavioral effects produced by systemic adrenergic agonists dexmedetomidine (0.1-3 nmol/g), clonidine (100-1000 nmol/g), epinephrine (1-30 nmol/g) and norepinephrine (10-300 nmol/g) were determined in Rana pipiens using the acetic acid test. Each agonist produced a dose-dependent analgesic effect that was sustained for at least 4 hr with all agonists. The analgesic effect of epinephrine and dexmedetomidine was observed 15 min after agonist administration and continued for more than 8 hr. Dexmedetomidine was the most potent agonist followed by epinephrine, norepinephrine and clonidine, and the relative potencies compared to epinephrine = 1.0 were 0.01 (clonidine), 0.02 (norepinephrine) and 4.83 (dexmedetomidine). Pretreatment with selective alpha-2 receptor antagonists, yohimbine and atipamezole, significantly decreased the analgesic effect of dexmedetomidine (80 and 87%) and clonidine (66 and 60%), whereas the selective alpha-1 receptor antagonist, prazosin, had no effect on dexmedetomidine but augmented clonidine analgesia. All animals treated with alpha adrenergic agonists retained corneal, righting and hind limb withdrawal reflexes and exhibited normal behavior. These studies demonstrate that systemic adrenergic agonists produce analgesia in amphibians, with a similar order of potency as reported in mammalian studies, and suggest that this analgesia is mediated by adrenergic alpha-2 receptors.
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PMID:Analgesic potency of alpha adrenergic agents after systemic administration in amphibians. 791 13

Intramuscular administration of medprotine, a protein fraction of human placenta (30-300 kDa), produced dose-dependent and long lasting analgesia as evaluated by various analgesic tests in mice. Activity was found in a dose range of 0.05-0.6 mg/kg in the phenylbenzoquinone and acetic acid writhing tests and 1.5-5 mg/kg in the hot-plate test. In this latter model, medprotine enhanced morphine-induced analgesia. Pretreatment with naloxone antagonized the effect of medprotine in all assays. The antinociceptive response of medprotine was not modified after a ten day pretreatment and no overt withdrawal symptom could be observed after either interruption of chronic treatment or administration of a precipitating dose of naloxone. It is concluded that the analgesic activity of medprotine may be mediated through either the opiate receptors or activation of endogenous opioidergic systems.
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PMID:Evidence for the involvement of opioidergic systems in medprotine-induced analgesia in the mouse. 792 91

In the rat hot plate test, vocalization induced by electric stimulation, tail flick test, and the mouse acetic acid writhing test, 3, 15-diacetylbenzoylaconine (DABA) ip exhibited a dose-dependent analgesic activity. Intrathecally (ith) administered DABA (527, 1186 micrograms.kg-1) had no analgesic action. Microinjection of DABA 35-75 micrograms.kg-1 or 20 micrograms into the cerebral ventricle (icv) or the periaqueductal gray (PAG) exerted a remarkable analgesic activity, which was abolished after bilateral lesions of locus coeruleus (LC). Microinjection of DABA (20 micrograms) into LC failed to produce apparent analgesic action. These results suggested that the sites of analgesia of DABA were mainly at the central supraspinal structures, and PAG was one of the primary sites, while LC was one of the intermediate links.
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PMID:[Sites of analgesic action of 3,15-diacetylbenzoylaconine]. 801 Jan 16

The relative analgesic potency of 11 opioid agents was assessed by using the acetic acid test in amphibians. Systemic administration of the mu agonists, fentanyl, levorphanol, methadone, morphine, meperidine and codeine; the partial mu agonist, buprenorphine; and the kappa agonists nalorphine, bremazocine, U50488 and CI-977 was made by s.c. injection into the dorsal lymph sac of the Northern grass frog, Rana pipiens. All agents produced a dose-dependent and long-lasting analgesia which persisted for at least 4 hr. The analgesic effects of single doses of each agent were significantly blocked or reduced by pretreatment with naltrexone. Systemic opioids produced log dose-response curves which yielded ED50 values ranging from 1.4 nmol/g for fentanyl to 320.9 nmol/g for nalorphine. Comparison of ED50 values gave a rank order of analgesic potency = fentanyl > CI-977 > levorphanol > U50488 > methadone > bremazocine > morphine > buprenorphine > meperidine > codeine > nalorphine. The relative analgesic potency of mu opioids in amphibians was significantly correlated with relative analgesic potency of these same agents obtained on the mouse writhing and hot plate tests. These data suggest that the amphibian model may serve as an adjunct or alternative model for the testing of opioid agents. Furthermore, given the inactivity of kappa opioids on rodent hot plate and tail-flick tests, the acetic acid test in amphibians may be especially well-suited for the assessment of opioid analgesia after administration of kappa-selective opioids.
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PMID:Analgesic potency of mu and kappa opioids after systemic administration in amphibians. 801 51

The newly synthesized 14-alkoxymetopon derivatives, 14-methoxymetopon, 14-ethoxymetopon, 14-methoxy-5-methyl-morphinone, exhibit high affinity for the naloxone binding sites in rat brain. A substantial decrease in affinity was observed, in the presence of NaCl indicating a high degree of agonist activity. All three 14-alkoxymetopon derivatives displayed high affinity for [3H][D-Ala2,(Me)Phe4,Gly-ol5]enkephalin ([3H]DAMGO) binding sites, much less potency toward delta sites and were the least effective at kappa sites. Isolated tissue studies using the guinea pig ileum preparation confirmed their high agonist potency. Following administration the new compounds produced naloxone reversible antinociceptive effects and were 130-300 times more potent than morphine in the acetic acid induced abdominal constriction model in the mouse, and the hot plate and tail flick tests in the rat. The compounds also produced dose-dependent muscle rigidity, and potentiated barbiturate-induced narcosis. The in vivo apparent pA2 values for naloxone against 14-ethoxymetopon and morphine were similar in analgesia, suggesting an interaction with the same (mu) receptor site. The dependence liability of 14-alkoxymetopon derivatives in the withdrawal jumping test was less pronounced than that of morphine in either rats or mice, similar to tolerance to the their analgesic action. It is concluded that the 14-alkoxymetopon derivatives studied are selective and potent agonists at mu opioid receptors, with reduced dependence liability.
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PMID:Highly potent novel opioid receptor agonist in the 14-alkoxymetopon series. 839 57


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