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)

Nalorphine is an unusual opiate. Whereas low doses of nalorphine antagonize morphine analgesia, higher nalorphine doses are analgesic, with ED50 values (95% CL) of 13.4 (11.5, 15.8) mg/kg in the writhing and 39.5 (26.6, 60.1) mg/kg in the tail-flick assay. Although nalorphine analgesia is sensitive to naloxone, implying an opioid mechanism, neither beta-funaltrexamine, naltrindole nor nor-binaltorphomine antagonized nalorphine analgesia in the tail-flick assay at doses which reversed equianalgesic doses of their respective selective agonists. Nalorphine and the kappa 3 opiate naloxone benzoylhydrazone demonstrated analgesic cross-tolerance regardless of whether the mice were treated chronically with either nalorphine or naloxone benzoylhydrazone. Animals tolerant to nalorphine were not tolerant to either morphine or U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(pyrrolindinyl)-cyclohexyl]- benzeneacetamide). Furthermore, nalorphine retained its analgesic potency in animals tolerant to U50,488H. Nalorphine exerts its analgesia predominantly through supraspinal mechanisms. Against systemically administered nalorphine, the opiate antagonist WIN44,441 ([2,6,11S-(-)-1-cyclopentyl-5-(1,2,3,4,5,6-hexahydro-8-hydroxy-3,6, 11-trimethyl-2,6-methano-e-benazocine-11-yl)-3-pentanone methylsulfonate) reversed nalorphine analgesia 1500-fold more potently when administered i.c.v. (ID50, 0.1 ng) than when given intrathecally (ID50,159 ng). Together these results indicate that nalorphine analgesia in the tail-flick assay does not involve mu, delta or the U50,488H-sensitive kappa 1 receptor and strongly suggest a role for supraspinal kappa 3 receptors.
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PMID:Pharmacological characterization of nalorphine, a kappa 3 analgesic. 185 Apr 62

1. The administration of an analgesic dose (10 mg/kg, s.c.) of morphine increased the concentrations of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brains of normal mice, and the time course of the change in the DOPAC concentration corresponded approximately to that of morphine analgesia. The increase in the concentration of the DOPAC induced by morphine (20 mg/kg, s.c.) was completely suppressed by nalorphine (2 mg/kg, s.c.) given 5 min after the morphine administration.2. In morphine-tolerant mice the concentrations of DOPAC and HVA in the brain did not differ from those observed in normal mice, and the increase in the concentrations of DOPAC and HVA in brain after the acute administration of morphine no longer occurred.3. Nalorphine (2 mg/kg) given alone did not cause any change in brain DOPAC and HVA concentrations in normal mice.4. The morphine-induced increase in DOPAC and HVA concentrations in the brain are discussed in the light of the hypothesis that dopamine might participate not only in the extrapyramidal motor system but also in the sensory mechanisms of the brain.
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PMID:Effect of morphine on the cerebral contents of metabolites of dopamine in normal and tolerant mice: its possible relation to analgesic action. 501 40

The experiments concerned the effects of glucuronate or sulfate conjugation at the 6-position of nalorphine on the analgesic and antagonistic activities and also on the development of tolerance and physical dependence. Nalorphine-3-and 6-sulfate ester were synthesized for the first time. The analgesic effect of nalorphine-6-sulfate and -glucuronide was higher than that of nalorphine when assessed in the acetic acid writhing test. However, these 6-conjugates exhibited less potent agonistic activity in the test with guinea-pig ileum muscle strip and revealed no analgesic effect in the tail pinch test. The antagonistic activity of these 6-conjugates to morphine analgesia was lower on their s.c. injection, but higher on i.c.v. injection than that of nalorphine. The development of tolerance to the analgesia caused by nalorphine was not affected by the 6-modifications. Frequent withdrawal signs were seen in mice treated chronically with anlorphine-6-conjugates by challenging with naloxone while mice treated with nalorphine showed no such signs. This potent enhancing effect of 6-conjugation on the development of physical dependence was suggested to be also the case with morphine. These changes of potency due to conjugation were interpreted as due to the altered interaction with multiple opioid receptors.
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PMID:Potentiation of physical dependence by conjugation at the 6-position of nalorphine. 654 Nov 41

1. The effects of N-methyl morphine and N-methyl nalorphine were studied on the hyperalgesia induced by prostaglandin E2 in the rat paw. Morphine and N-methyl morphine injected intraperitoneally (2-8 mg/kg) caused a dose-dependent analgesia. The potency of N-methyl morphine was of the same order of magnitude as its parent compound in causing analgesia. 2. Nalorphine caused a short-lasting analgesia followed by an enhancement of prostaglandin-induced hyperalgesia. In contrast, its analogue, N-methyl nalorphine, injected intraperitoneally, induced analgesia but did not enhance the hyperalgesia induced by prostaglandin E2 or induce hyperalgesia in the control paw. 3. Treatment of the animals with N-methyl nalorphine at a dose which had no apparent analgesic effect antagonized the analgesic effect of morphine or N-methyl morphine. 4. Administration of a low dose of N-methyl nalorphine into the paw totally antagonized the analgesic effect of N-methyl morphine administered either locally into the paw, or intraperitoneally. 5. It is concluded that quaternary analogues of morphine and nalorphine, which do not have central effects because they do not cross the blood-brain barrier, retain the peripheral analgesic effects of the parent compounds.
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PMID:The analgesic effect of quaternary analogues of morphine and nalorphine. 696 50

24 hartebeests (Alcelaphus buselaphus major), one waterbuck (Kobus defassa) and 16 kobs (Kobus kob) were immobilized during field work in Upper Volta. The use of the newly developed piperidine derivative R 33799 at weight treated dosage levels can be strongly recommended for the immobilisation of hartebeest. In this species the drug produces a sufficient deep analgesia within a reasonable short period for all handling purposes. It is safe, has a wide therapeutic index, can be used in syringes of not more than 1 ml capacity and is quickly reversed by the antidote (nalorphine hydrobromide). No fatalities occurred. The limited number of kobs immobilized did not allow final conclusions to be drawn on the compatibility of the drug for this game species unless the central nervous side effects as described can be explained better and overcome. Further investigation should be undertaken to study the reaction of kob to lower dosages of R 33799 and other combinations of this analgesic with other neuroleptics. Nalorphine hydrobromide proved to be a useful antidote in hartebeest, but less effective in kob.
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PMID:On the immobilization of hartebeest and kob in Upper Volta. 719 87

Evidence is presented that the receptors responsible for the mediation of analgesia by morphine-like drugs are similar to those which are involved in the production of a reversible lenticular opacity. The activity of a number of compounds in mice on the lens was closely correlated with analgesic potency in this species. Stereospecificity for isomers with D configuration was demonstrated for both effects. Nalorphine only antagonized the lenticular opacity activity of those drugs the analgesic action of which it abolished.
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PMID:Similarly between receptors responsible for the production of analgesia and lenticular opacity. 1400 75

A quantitative investigation has been made of the antagonism by nalorphine of the analgesia and lenticular opacity produced in mice by a number of compounds. ED50 values have been obtained for each drug in the absence and in the presence of increasing doses of nalorphine, and from these, appropriate dose-ratios have been calculated. It has been possible to derive the equivalent of a pA(2) value for each drug with nalorphine and, since these are almost identical, it may be concluded that all the drugs combine with similar receptors. Nalorphine antagonizes both actions by competing for the receptors. It was not possible to antagonize quantitatively the analgesic action of pethidine with nalorphine, although the lenticular effect could be abolished. The effect of nalorphine on the change in skin temperature in mice induced by some of the analgesic drugs was also investigated.
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PMID:QUANTITATIVE STUDIES OF THE ANTAGONISM BY NALORPHINE OF SOME OF THE ACTIONS OF MORPHINE-LIKE ANALGESIC DRUGS. 1419 Apr 64