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 role of the GABAergic system in the analgesic action of prolactin was investigated using a pharmacological approach. 2. THIP, a GABAmimetic, per se produced an analgesic effect and potentiated the analgesic effect of prolactin and morphine. 3. Bicuculline, in subconvulsive doses, per se did not alter the number of writhings, while it attenuated the analgesic effect of prolactin. 4. These results indicate a positive role for the GABAergic system in prolactin induced analgesia. 5. Since THIP resembles morphine and because prolactin possesses several other morphine-like functions, it is possible that the role played by GABA may be an opioid-related one.
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PMID:Role of GABAergic system in prolactin analgesia. 261 65

1. The interactions of three GABAergic compounds, gamma-acetylenic GABA, gamma-vinyl GABA and ethylenediamine with the analgesic effects of morphine and pentazocine were examined in mice using the hot plate and tail immersion tests. 2. A significant increase in reaction time induced by morphine was noted in the tail immersion test after pretreatment with the drugs acting through GABA functions. 3. The inhibitors of GABA transaminase, gamma-acetylenic GABA and gamma-vinyl GABA, and the GABAmimetic ethylenediamine did not significantly change the analgesic action induced by pentazocine. 4. In the hot plate test the three GABAergic compounds antagonized the analgesic effects of pentazocine in contraposition with previous results indicating that morphine-induced analgesia is increased by pretreatment with those agents. 5. These findings suggest that GABAergic and opiopeptidergic systems are interconnected through mu receptors, whereas the kappa opiate systems seem to be unrelated to GABA functions.
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PMID:A comparison of GABAergic influences on the analgesic responses to morphine and pentazocine. 271 13

In rats anaesthetised with alphaxalone/alphadolone (Saffan), bilateral microinjections of the GABA antagonist, bicuculline, into a restricted region of nucleus paragigantocellularis lateralis (PGL), ventromedial to the caudal pole of the facial nucleus, produced an increase in the latency of the tail flick response to noxious heat. The analgesia was always accompanied by a rise in mean arterial blood pressure but the time course of the cardiovascular and antinociceptive changes was different. Guanethidine (7 mg/kg i.v.) blocked the pressor response but had no effect on the magnitude or time course of the analgesia. In contrast, microinjection of physostigmine into PGL produced a pressor response but no change in the latency of the tail flick response. It is concluded that there are functionally distinct pools of neurones within PGL which respectively produce antinociception and changes in vasomotor activity. Ongoing activity in both types of neurone is regulated by a tonic inhibitory GABAergic influence. In addition, the cardiovascular neurones receive a tonic excitatory cholinergic input.
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PMID:Tonic GABAergic and cholinergic influences on pain control and cardiovascular control neurones in nucleus paragigantocellularis lateralis in the rat. 282 91

The experiments on rats have shown that repeated administration of depakin and baclofen induced the development of tolerance to their antinociceptive effect. The animals tolerant to depakin and baclofen were supersensitive to the analgetic effect of morphine and clonidine in tail-flick test. In vocalization test the analgetic effect of clonidine in baclofen- and depakin-tolerant animals was not altered. The antinociceptive effect of morphine under these conditions was reduced significantly in depakin-tolerant rats and was unchanged in baclofen-tolerant animals. The role of opioid and adrenergic mechanisms in GABA-ergic analgesia and in the development of tolerance is discussed.
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PMID:[Role of opioid and adrenergic mechanisms in the analgesic action of GABA-positive drugs]. 283 4

In the cat there is no convincing evidence that a particular compound mediates a supraspinal control of spinal transmission of nociceptive information. There is good evidence that opioid peptides are released segmentally in response to nociceptive input to the spinal cord and that this acts to inhibit motoneurons and to reduce transmission of nociceptive information to supraspinal areas. In the cat there is no evidence that stimulation at supraspinal sites producing analgesia results in a spinal release of opioid peptides. In the rat evidence for the latter has been obtained but there are no data from other species. Tonically present supraspinal inhibition of spinal transmission of nociceptive information in the cat does not involve opioid peptides. Indirect evidence favours a role for 5-hydroxytryptamine and noradrenaline in supraspinal control of spinal processing of nociceptive transmission. Peripheral antagonists of 5-HT have reduced spinal inhibition from stimulation at supraspinal sites but the site of action is unknown. Progress with noradrenaline involvement has been hindered by lack of a suitable antagonist. Although the amino acids, glycine and GABA are involved in segmental inhibition of transmission of nociceptive information, no convincing evidence has indicated their involvement in supraspinal controls.
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PMID:Pharmacology of descending control systems. 285 90

The influence of Ro 15-1788 and bicuculline on the action of GABA-positive drugs (muscimol), GABA cethyl ester, piracetam and depakine and benzodiazepine tranquilizers (diazepam, phenazepam) on motivated aggression has been studied. It has been shown that Ro 15-1788 which has a weak antiaggressive effect selectively antagonizes the anti-aggressive effect of tranquilizers but not that of GABA-positive drugs. Bicuculline antagonizes antiaggressive activity of the drugs of both types. The action of these antagonists on the effect of the drugs under study as regards the analgetic activity of morphine was also studied. It has been shown that Ro 15-1788 antagonizes the potentiation of morphine analgesia caused by diazepam. At the same time Ro 15-1788 does not influence morphine analgesia potentiated by muscimol. Bicuculline removes the potentiation of morphine analgesia caused both by diazepam and muscimol it is concluded that bicuculline-sensitive GABA receptors modulate the antiaggressive effect of benzodiazepines and their influence on the analgetic action of opiates.
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PMID:[Antagonism of RO 15-1788 with benzodiazepines in the effect on motivated aggression and the action of analgesics]. 285 59

We evaluated the anxiolytic property of a brain-specific gamma-aminobutyric acid delivery system (GABA-CDS) in male rats by means of a drink-foot shock conflict procedure. Brain-specific delivery of the active compound was achieved by combination of GABA benzyl ester with an interconvertible dihydropyridine in equilibrium pyridinium salt carrier, which is "locked in" to the brain upon its oxidation. Pharmacokinetic studies revealed that the hydrophilic pyridinium salt form (G-Q+) of the GABA-CDS formed in situ remained in the brain for 12 h but was cleared from the blood and other peripheral tissues by 0.5-4 h. While the lipophilic form (G-DH) of the GABA-CDS caused a marked and sustained anxiolytic response when administered systemically, GABA and the charged pyridinium salt (G-Q+ form) of the GABA-CDS were ineffective. G-DH was injected at either 0, 4, 10 or 25 mg/kg IV in DMSO after rats were water and food deprived. After either 0.5, 2, 4, 8 or 24 h, rats were permitted 10 s of shock-free drinking of 10% sucrose, then given a 35 mA (DC) current through the drinking tube. Drinking time was recorded for 3 min. All doses of G-DH caused a significant increase in anxiolysis over control levels through 8 h. An increase (4 to 7-fold) in anxiolytic activity was observed through the 10 mg/kg dose with the 25 mg/kg dose causing no additional increase. No sedation or analgesia was observed at 2 h with any anxiolytic-producing dose of G-DH. These results suggest that G-DH elicits anxiolysis with minimal sedation, through the local brain action the G-Q+ or subsequent to the release of GABA.
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PMID:Anxiolytic activity of a brain delivery system for GABA. 288 84

NE-19550, N-(3-methoxy-4-hydroxybenzyl)oleamide, is a capsaicin analogue that has been shown to possess oral activity in the 55 degrees C rat hot-plate and mouse phenylquinone abdominal constriction analgesia tests. The compound also displayed anti-inflammatory activity orally in the carrageenan-inflamed rat-paw test and topically in the croton oil-inflamed mouse-ear test. NE-19550 activity in the thermal analgesia assay was not blocked by the opioid antagonist naloxone, and no inhibition of prostanoid synthesis in rat platelets or tissues was seen following a high analgesic and anti-inflammatory oral dose (300 mg/kg). A wide variety of known neuronal antagonists (adrenergic, serotonergic, dopaminergic, cholinergic, GABA-ergic, histaminergic) were found not to inhibit NE-19550 analgesia, further indicating a lack of involvement of known drug receptors mediating analgesic responses. Analgesic doses of NE-19550 were also found to lack the acute toxicity and thermoregulatory desensitization characteristics of the parent natural product capsaicin. It appears to represent a new class of potent-acting, non-narcotic, anti-inflammatory analgesic agents.
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PMID:NE-19550: a novel, orally active anti-inflammatory analgesic. 296 May 11

Drugs affecting various steps of GABA transmission exhibit analgesia in a variety of experimental models in animals; this analgesic response generally requires high doses of the drugs and does not appear to be opiate-like since the GABAergic analgesia is naloxone-insensitive and lacks dependence liability. The outcome of the analgesia response is variable when opiate and GABAergic drugs are administered together; however, directly acting GABA receptor stimulants and GABA-transaminase inhibitors generally enhance the analgesic effect of opiates. The development of newer GABAergic drugs with greater potency and specificity may offer an alternative to opiate analgesics. The results obtained over the years, on the possible involvement of the GABA system in morphine tolerance and dependence are equivocal. Studies on region-specific changes in opiate-GABA interaction as well as opiate-GABA-benzodiazepine interaction are needed to further elucidate the role of GABA on opiate system.
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PMID:GABA in morphine analgesia and tolerance. 298 43

Diazepam within its therapeutic dose range, was shown to have no effect on nociception, but was shown to antagonize the analgesic action of morphine. This antagonism was found to be statistically significant at 0.5 mg/kg diazepam. To elucidate the mechanism of this inhibitory action of diazepam against morphine analgesia, Ro 15-1788, the specific antagonist of benzodiazepine receptors was used. As a result, Ro 15-1788 was found to partially reverse the inhibitory action of diazepam against morphine analgesia. This overall interaction between the supramolecular GABA receptor complex and morphine is discussed.
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PMID:The possible role of benzodiazepine receptors in morphine analgesia. 301 93


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