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)

Experiment 1 showed that intravenous administration of [D-Ala2]-methionine enkephalinamide resulted in dose-dependent inhibition of the tail-flick reflex, mild hypotension, and bradycardia. The enkephalinamide-induced inhibition of the tail-flick reflex and cardiovascular effects were eliminated in the bilateral cervical vagotomized anesthetized rat preparation, but were unaffected by either a unilateral right vagotomy or bilateral sinoaortic deafferentation in the conscious rat preparation. Experiment 2 demonstrated that the antinociceptive and cardiovascular actions of enkephalinamide were eliminated by pretreatment with intravenous administration of the opioid-receptor antagonist naloxone. These experiments strongly suggest that peripherally circulating enkephalins could reflexively induce analgesia by activating cardiopulmonary receptors whose afferents travel in the vagi.
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PMID:[D-Ala2]-methionine enkephalinamide reflexively induces antinociception by activating vagal afferents. 649 13

Changes in responsiveness for the stinging reaction of honeybees fixed in a holder after receiving 3 electrical shocks delivered with 1 min interval, was registered and used as measurement for the effect of 2 microliter of different solutions injected. Every shock consisted of a train of pulses of 1 msec each, delivered for 2 sec at a frequency of 100 Hz. Injection of morphine-HCl (50 to 200 n-moles/bee) produced a dose dependent reduction of the honeybee stinging response to the electrical shocks. The morphine dose that produced a 50% inhibition of the response (D50) was 148 n-moles/bee (927 micrograms/g), i.e., a value far greater than that reported for vertebrates in behavioral test of analgesia. Naloxone 1.1 micrograms/g produces a significant reduction of morphine D50 effect and at 4-5 micrograms/g, a full disinhibition. Thus, whereas the D50 of morphine for honeybees is far greater than that for vertebrates, the doses of naloxone that antagonize morphine are similar for bees and vertebrates. Possible explanations of this difference are mentioned. Injections of met-enkephalin, leu-enkephalin, kyotorphin and (D-Ala2) methionine-enkephalinamide, given in doses of 200 n-moles/bee, an amount greater than that of the morphine D50, exhibited no effect on the stinging response.
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PMID:The stinging response of the honeybee: effects of morphine, naloxone and some opioid peptides. 665 18

The possibility that divalent cations may antagonize opiate peptide analgesia and stress-induced analgesia was examined. Intracerebroventricular injection of low doses of Ca2+, Mn2+ and Mg2+ antagonized beta-endorphin and methionine-enkephalin analgesia. Ba2+ and Cd2+ were without effect. The ionophore, A23187, significantly antagonized beta-endorphin analgesia and the effect was increased when a low dose of Ca2+ was injected at the same time as the ionophore. Ethylene glycol tetraacetic acid (but not ethylenediamine tetraacetic acid) significantly potentiated endorphin analgesia. Stress-induced analgesia, as determined by increased tail-flick latencies following intraperitoneal injection of acetic acid, was effectively antagonized by naloxone, Ca2+ and Mn2+. The frequency of writhing following acetic acid injection was increased by both naloxone and divalent metal ions, again suggesting antagonism of endogenous opiates. These results confirm previous findings indicating that divalent metal ions (and especially Ca2+) may be involved in the actions of opiates.
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PMID:Modification of endorphin/enkephalin analgesia and stress-induced analgesia by divalent cations, a cation chelator and an ionophore. 682 Nov 93

Four analogs of enkephalin (EK) have been synthesized by the solid-phase method and their biological activities have also been investigated. All four analogs were less active than Met-enkephalin (Met-EK) as shown by relative potencies in the guinea pig ileum (GPI) assay: Met-EK, 100; [Phe5]-EK-NH2, 59; [Trp5]-EK-NH2, 11; Met-EK-Cys(Cam)-OH, 37; and N,N'-bis(Met-EK)-cystine, 34. Two of the analogs were more potent than Met-EK as shown by relative potencies in the mouse tail-flick assay for analgesia: Met-EK, 100; [Phe5]-EK-NH2, 1340; [Trp5]-EK-NH2, 1640. Quantitative structure-activity relationship calculations were carried out for GPI potencies of analogs substituted in position 5. The calculation indicated that, in this position, the bulkiness had the main influence.
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PMID:Enkephalin analogs: synthesis and properties of analogs with lipophilic or extended carboxyl-terminus. Quantitative structure-activity relationship of analogs modified in residue position 5. 686 64

Intravenous injection of opiate agonists produces in the rat a precipitous but transient fall in heart rate. This bradycardia, which may be a vagal chemoreflex, appears to originate from peripheral opiate receptors because the onset is faster after injections of morphine into the peripheral circulation than after central injections. The bradycardia is blocked by i.v. administration of tertiary and quaternary naloxone at doses which are not effective centrally. Tolerance develops to morphine bradycardia after s.c. infusions of morphine sulfate (e.g., 74 nmol/hr/rat s.c. for 2 days elevated the morphine ED50 by 22 times), but not after central infusions of morphine at doses which are sufficient to produce physical dependence and tolerance to morphine analgesia. Subcutaneously infused morphine animals are cross-tolerant to FK33,824 (Tyr-D-Ala-Gly-NMePhe-Met(O)-ol), a potent enkephalin analog, and vice versa, but are not tolerant to serotonin or phenyldiguanide. Vagal bradycardia may be a convenient index for studying the peripheral action of opioid agonists.
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PMID:Tolerance to morphine bradycardia in the rat. 686 38

Metkephamid is an analog of methionine enkephalin. The efficacy, safety, and time course of analgesia with 70 or 140 mg metkephamid were compared with those of 100 mg meperidine and placebo in 59 hospitalized women with severe postpartum episiotomy pain. There were two separate trials with single intramuscular doses and identical designs, including parallel groups, randomized blocks, and double-blind conditions. Using subjective reports as indexes of response, patients rated pain intensity, pain relief, and side effects at periodic interviews for 6 hr. Almost all measures of summed and peak analgesia exhibited important differences among the three treatments in both trials. Metkephamid at the 140-mg dose was the most effective and meperidine, 100 mg, was next, whereas metkephamid, 70 mg, and placebo were least effective. Only metkephamid, 140 mg, and meperidine were measurably superior to placebo. Both treatments took effect within 30 min and peaked at 1 to 2 hr; with 140 mg metkephamid, maximum analgesia was sustained 6 hr, i.e., 2 hr longer than with meperidine. Metkephamid, 70 mg, could not be distinguished from placebo throughout its entire time course. Although dizziness was experienced with meperidine, the two metkephamid doses induced other side effects, including sensation of heavy limbs, dry mouth, eye redness, and nasal stuffiness. None were distressing. Our results suggest that 140 mg metkephamid compares favorably with 100 mg meperidine for analgesia after episiotomy, but it induces minor side effects more frequently.
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PMID:Metkephamid and meperidine analgesia after episiotomy. 687 19

[Met]Enkephalin-Arg6-Phe7 is an opiate-like peptide normally found in the the adrenal gland and brain that has analgesic (antinociceptive) activity when administered directly into the cerebral ventricles of mice. On a molar basis, [Met]-enkephalin-Arg6-Phe7, with a median effective dose (ED50) of 38.5 nmol/mouse, is 8 times more potent than [Met]enkephalin. As with [Met]enkephalin, analgesic activity is blocked by naloxone and intravenous administration does not produce characteristic opiate effects in tests for analgesic, antidiuretic, or antidiarrheal activity. These findings suggest that [Met]enkephalin-Arg6-Phe7 may be at least as important as the enkephalins in the postulated enkephalin system mediating pain and analgesia.
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PMID:Analgesic activity of the naturally occurring heptapeptide [Met]enkephalin-Arg6-Phe7. 693 69

We have synthesized enkephalin analogues in which C-terminal methionine or leucine residues are replaced by a second active fragment of the enkephalin analogue. Synthesis of two compounds is described: in one, two fragments of a D-Ala2-enkephalin analogue are connected by a -NH-NH-bridge, and in the other, three methylene groups are incorporated between the amino groups. The first compound is a very potent inhibitor of electrically induced contractions of guinea-pig ileum and produces a strong analgesia when administered intraperitoneally in mice. The second compound is less active on the ileum and fails to produce analgesia after systemic injection. The double-enkephalins may interact with mu-receptors.
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PMID:Double-enkephalins--synthesis, activity on guinea-pig ileum, and analgesic effect. 713 34

Nicotine produced a distinct reproducible syndrome in the conscious dog when injected intravenously or intracerebroventricularly. Intravenously administered nicotine (40 micrograms/kg/min for 20 minutes) increased cardiac and respiratory rates and produced analgesia, miosis, hypothermia, behavioral restlessness and emesis. When microinjected into the third cerebral ventricle, nicotine (100-200 micrograms) similarly increased cardiac and respiratory rates and pupillary diameter; and produced behavioral restlessness, emesis, erratic analgesia and maintained wakefulness and a desynchronized EEG. Microinjection of nicotine (5-25 micrograms) into the periaqueductal gray failed to alter any of the parameters studied. Intravenous pretreatment with the opioid antagonist naltrexone (2 mg/kg) influenced the action of intravenous nicotine on certain physiological systems. While naltrexone alone produced a significant degree of tachycardia, miosis, and analgesia, it potentiated the tachypnea and antagonized the miotic response evoked by nicotine. Methionine-enkephalin was detected in perfusates obtained from the lateral cerebral ventricles of conscious dogs. Nicotine produced a non-significant decrease in enkephalin levels. These observations suggest that there are interactions between endogenous opioid and nicotinic processes. However, they are complex and may differ from one functional system to another.
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PMID:Interaction between nicotine and endogenous opioid mechanisms in the unanesthetized dog. 717 83

Intracerebroventricular (i.c.v.) administration of subanalgesic doses of beta- and leucine-endorphin in mice 15 min before subcutaneous morphine injection, significantly enhanced the analgesic effects of the morphine as measured by the tail-flick assay. A similar effect was seen with levorphanol analgesia but not enhancement of leucine- or methionine-enkephalin analgesia by beta-endorphin was observed. The same doses of the endorphins did not affect the development of single-dose morphine tolerance and dependence. Leucine-enkephalin failed to affect morphine analgesia, tolerance or dependence development, while low doses of methionine-enkephalin administered i.c.v. were observed to have an antagonistic effect on morphine analgesia without affecting tolerance or dependence development. Neither endephalin had any effect on beta-endorphin analgesia.
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PMID:Methionine-enkephalin antagonism and endorphin potentiation of narcotic-induced analgesia. 719 Sep 25


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