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)

For various opioid agonists (n = 35) an unsatisfactory correlation between analgesic activity in vivo (mouse) and receptor binding affinity (rat brain) in vitro was obtained. Excellent correlations were observed, however, after separation of the opioid agonists into two groups with mu- and kappa-receptor selectivity, respectively. The correlation of the analgesic potency with the affinity to the opioid kappa-receptor was very high for the group of kappa-agonists, while it was low for the group of mu-agonists. The slopes of the regression lines were near unity and parallel. The shift from the less potent mu-agonists to the more potent kappa-agonists was about one order of magnitude indicating that analgesia of kappa-agonists is mediated by both mu- and kappa-receptors.
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PMID:Differentiation of mu- and kappa-receptors by means of correlation of analgesic potency in vivo and receptor binding affinity in vitro of various opioid agonists. 609 51

Prolyl-leucyl-glycinamide (PLG) at a low dose (10 ng/mouse) administered by an intracerebroventricular (i.c.v.) injection did not affect levorphanol analgesia, but PLG at higher doses (10 and 100 micrograms/mouse) and alpha-melanocyte-stimulating hormone (alpha-MSH) (10 ng/mouse) antagonized levorphanol analgesia. Development of levorphanol tolerance was facilitated by 10 ng/mouse of PLG, unaffected by 10 micrograms/mouse of PLG, but antagonized by 100 micrograms/mouse of PLG and 10 ng/mouse of alpha-MSH. The effect of PLG on levorphanol dependence was assessed by changes in body weight and temperature during naloxone-induced withdrawal. PLG (10 ng/mouse) facilitated the development of levorphanol dependence, but 10 micrograms/mouse of PLG had no effect. PLG (100 micrograms/mouse) antagonized development of levorphanol dependence. PLG at doses of 10 and 100 micrograms/mouse precipitated withdrawal in levorphanol-dependent mice. alpha-MSH (10 ng/mouse) antagonized development of levorphanol dependence as evidenced by an increase in the ED50 of naloxone required to induce withdrawal jumping. These results indicate that PLG and alpha-MSH affected levorphanol-induced analgesia, tolerance and dependence in a qualitatively similar manner to their effect on morphine-induced analgesia, tolerance and dependence.
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PMID:Effect of prolyl-leucyl-glycinamide and alpha-melanocyte-stimulating hormone on levorphanol-induced analgesia, tolerance and dependence. 614 83

Prolyl-leucyl-glycinamide (PLG) at a low dose (10 ng/mouse) administered intracerebroventricularly (i.c.v.) did not affect morphine analgesia, but produced a greater increase in the ED50 of morphine-pretreated (100 mg/kg of morphine sulfate) mice as compared to control mice. PLG at doses of 10 and 100 micrograms/mouse antagonized morphine analgesia. Development of morphine tolerance was unaffected by 10 micrograms/mouse but antagonized by 100 micrograms/mouse of PLG. Development of morphine dependence was assessed by changes in body weight and temperature during naloxone-induced withdrawal. PLG (10 ng/mouse) potentiated, 10 micrograms/mouse had no effect and 100 micrograms/mouse antagonized development of morphine dependence. PLG at doses of 10 and 100 micrograms/mouse precipitated withdrawal in morphine-dependent mice. When mice were pretreated with 1.0 mg/kg naloxone i.p. 15 min before PLG, all doses of PLG had no effect on morphine analgesia, but potentiated the development of morphine tolerance and dependence. None of the doses of PLG altered whole brain levels of morphine. PLG did not alter the affinity of opioid receptors for etorphine or the maximal number of binding sites but PLG did exhibit a very weak affinity for opioid receptors. These results indicate that PLG potentiated development of morphine tolerance and dependence through a mechanism not involving opioid receptors. However, at very high doses it was a weak opioid receptor antagonist.
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PMID:Dose-dependent effects of prolyl-leucyl-glycinamide on morphine-induced analgesia, tolerance and dependence. 614 43

The 6-bis(2)chloroethyl)amino derivatives of oxymorphone and naltrexone, chloroxymorphamine (COA) and chlornaltrexamine (CNA), respectively, produce an irreversible inhibition of [3H]naltrexone binding to mouse brain homogenates. Intracerebroventricular (i.c.v.) injection of COA (4 nmol/mouse) elicits analgesia which lasts 4 times longer than analgesia produced by equimolar and equieffective dose of oxymorphone. The analgesia induced by COA can be reversed and blocked by naloxone. Injections of both COA and CNA i.c.v. antagonize morphine-induced analgesia for 3 days. Similarly, when [3H]naltrexone binding is measured in brains from mice pretreated i.c.v. with COA or CNA, there is a significant decrease in total specific binding for 3 days after pretreatment. These data suggest that CNA and COA alkylate the opioid receptors to produce antagonist and agonist-antagonist effects, respectively. The implications of these findings are discussed with respect to their effect on our perception of the opioid receptor-narcotic agonist interaction and the mechanisms of tolerance and dependence.
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PMID:Pharmacological studies with an alkylating narcotic agonist, chloroxymorphamine, and antagonist, chlornaltrexamine. 616 47

In the tail-flick test in mice, the intraventricular administration of Substance P (10-5,000 ng/mouse) produced a naloxone-reversible analgesic effect of rapid onset and long duration. The dose-response curve was bell-shaped, the analgesic effect being smaller after the largest doses. The analgesia was blocked by concomitant intraventricular administration of the antibody against met-enkephalin but not by the antibody against beta-endorphin. In the hot plate assay, Substance P produced analgesia in mice with high sensitivity to pain, and hyperalgesia in mice with lower sensitivity to pain than normal. The analgesia was blocked by the antibody against met-enkephalin but the hyperalgesia or the scratching response were not modified by the antiserum. The results appear to indicate a dual effect, analgesic or hyperalgesic, of Substance P in mice, the former probably being mediated by release of met-enkephalin.
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PMID:Blockade by met-enkephalin antiserum of analgesia induced by substance P in mice. 618 74

The current study was conducted in order to explore the effects of repeated naloxone administration as a function of food intake. Rats were trained to press a bar to avoid foot-shock. They were allowed either free or restricted access to food. Free-feeding rats developed a strong sensitivity to naloxone, as manifested by an increased shock rate after naloxone injection. When animals were food-deprived, the sensitivity was greatly reduced. A different species (mouse) and two different tests were used to examine further the effects of food intake and pretreatment with naloxone. The mice were given either free access to food or a restricted diet and were pretreated with either naloxone or saline. The effects of food intake and pretreatment with naloxone were examined in terms of motor activity, morphine analgesia and naloxone hyperalgesia. The results showed that prior exposure to naloxone in free-feeding animals enhanced the suppressant effect of naloxone on motor activity and the analgesic effects of morphine (as measured by paw-lick, but not as measured by jump in the hot-plate test), but had no effect on the hyperalgesic effect of naloxone. When mice were food-deprived during naloxone administration, sensitization did not occur. The hypothesis that naloxone sensitivity is due to changes in the number of brain opiate receptors was tested by measuring the number and affinity of [3H]naloxone binding sites on brain membranes from mice chronically treated with naloxone. Neither naloxone pretreatment nor food deprivation affected the number or affinity of binding sites. The gamma-aminobutyric acid antagonist effect of naloxone (as measured by gamma-[3H]aminobutyric acid binding) was also unchanged by naloxone pretreatment. Thus, the basis of the interactions between naloxone and the feeding state remains unclear.
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PMID:Sensitization produced by repeated administration of naloxone is blocked by food deprivation. 628 15

The carboxy-terminal nonacosapeptide sequence of porcine preproenkephalin B contains the sequence of Leu-enkephalin at its amino terminus. The endogenous existence of this peptide, leumorphin, has not yet been proved. Synthesis of leumorphin was carried out by a solid-phase technique and the purity and structure of the synthetic peptide were confirmed. Synthetic porcine leumorphin exhibited a dose-dependent opiate effect (ED50 4.70 X 10(-9) M) on electrically stimulated contraction of the guinea pig ileum preparation. The potency was about 100 times as high as that of Leu-enkephalin. Leumorphin was less potent than dynorphin(1-13) (ED50 0.38 X 10(-9) M) but it was more active than beta h-endorphin (ED50 18 X 10(-9) M). The opiate activity was only partially reversed by naloxone. Intracisternal injection of synthetic leumorphin caused significant analgesia in mice (ED50 7.31 nmol/mouse). The potency was lower than that of beta h-endorphin (ED50 0.60 nmol/mouse) but higher than that of dynorphin(1-13) (ED50 16.10 nmol/mouse). Intracisternally injected leumorphin did not produce such a violent behavioral effect as did dynorphin(1-13), and it exhibited a mild sedative effect. The data supports the concept that leumorphin is a new type of opioid peptide and that the synthetic preparation will be useful for further biological and immunological studies on this peptide.
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PMID:Synthesis of porcine leumorphin and some of its biological activities. 630 16

Intrathecal administration of morphine, levorphanol, bremazocine, ethylketocyclazocine or [D-Ser2,Leu5,Thr6]enkephalin to rats, at doses 10-50 times greater than that necessary to elicit analgesia in the tail flick test, had no marked effect on gastrointestinal transit as determined by the charcoal meal test. In contrast, intrathecal administration of various doses of morphine to mice significantly antagonized transit (A50 (that dose which inhibited transit to 50% of controls) = 14.7 (0.71-2.89) micrograms/mouse). These results suggest (1) a lack of involvement of opioid sensitive spinal structures in the control of gastrointestinal transit in rats, and (2) a species difference in the slowing effect of intrathecal morphine on gastrointestinal transit.
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PMID:A species difference in the slowing effect of intrathecal morphine on gastrointestinal transit. 668 54

1. CAM--a new type of opiate antagonist [10, 11] was used to study the types of opiate receptors (OR) involved in the analgesic and narcosis potentiating effects of different opiates. The analgesic assays were: hot plate, algolytic test (rat) and acetic acid stretching test (mouse). 2. The in vivo equivalent of pA2 value (apparent pA2) for naloxone (NX) and CAM was determined with each opiate agonists. 3. The estimated pA2 values for analgesia did not differ significantly from those obtained for anesthesia in the case of NX, however, if CAM was used as antagonist the pA2 values were the same as with NX in the algolytic test, but different result was obtained when analgesia was measured by hot plate and stretching test, and narcosis potentiation was examined. 4. It was concluded that NX and CAM interact with the same OR when algolytic test was used, however different type of OR might be involved in hot plate and stretching assays and anesthesia potentiation, too.
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PMID:Quantitative studies of the antagonism by naloxone and N-cyclopropylmethyl-norazido-dihydroisomorphine (CAM) of different opiates. 689 45

1. A single i.p. dose of taurine (25 mg/mouse) given to mice 3 hr before an i.p. injection of morphine (0.1 mg/mouse) decreased the analgesic response of the animals to morphine. 2. Neither a lower dose of taurine nor the same dose of another amino acid was effective. 3. The analgesic response to morphine was also reduced by inclusion of taurine in the drinking water. 4. The results of the present study indicate that peripherally administered taurine antagonized morphine-induced analgesia, similar to a previous report that taurine administered centrally, diminished the analgesic response to a centrally injected opioid peptide.
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PMID:Peripheral administration of taurine antagonizes morphine-induced analgesia in mice. 848 14


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