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)

In the present study, the mechanism of the antagonistic action of 0.5 mg/kg diazepam on the analgesic effect of morphine was investigated. While Ro 15-1788, a benzodiazepine receptor antagonist, was found to partially reverse the inhibitory action of diazepam on morphine analgesia, a chloride channel blocking agent, picrotoxin, produced complete antagonism of the action of diazepam. Furthermore, picrotoxin potentiated the partial antagonistic effect of Ro 15-1788 at a normally ineffective dose to affect the 0.5 mg/kg diazepam-morphine dose-response curve. These overall effects of picrotoxin on the supramolecular GABA receptor complex are discussed.
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PMID:The possible modulation of morphine analgesia by the supramolecular GABA receptor complex. 302 98

It was shown in experiments on rats that the analgesic effect of GABA-positive drugs is followed by sedative and myorelaxant manifestations, however there is no direct relationship between the effects. Bicuculline significantly attenuates analgesia induced by THIP, gamma-acetylenic-GABA and depakin in the test of vocalization but enhances their analgesic activity in the tail-flick test. The involvement of individual subtypes of GABA receptors in mediation of analgesic and general depressant effects of GABA-positive drugs was discussed.
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PMID:[Comparative study of the analgesic, sedative and myorelaxant effects of GABA-positive preparations]. 303 Aug 2

Both directly acting (GABAA and GABAB agonists) and indirectly acting GABAergic agents (GABA uptake inhibitors and GABA-transaminase inhibitors) produce analgesia in a variety of animal test systems. Analgesia produced by GABAA agonists is probably due to a supraspinal action, although spinal sites may also play a role. GABAA agonist analgesia is insensitive to naloxone, bicuculline, picrotoxin and haloperidol, but is blocked by atropine, scopolamine and yohimbine suggesting a critical role for central cholinergic and noradrenergic pathways in this action. The lack of blockade by the GABAA antagonist bicuculline is difficult to explain. Both bicuculline and picrotoxin have intrinsic analgesia actions which may not necessarily be mediated by GABA receptors. The GABAB agonist baclofen produces analgesia by actions at both spinal and supraspinal sites. Baclofen analgesia is insensitive to naloxone, bicuculline and picrotoxin, and blockade by cholinergic antagonists occurs only under limited conditions. Catecholamines are important mediators of baclofen analgesia because analgesia is potentiated by reserpine, alpha-methyl-p-tyrosine, phentolamine, ergotamine, haloperidol and chlorpromazine. A role for serotonergic mechanisms is less well defined. Methylxanthines, which produce a clonidine-sensitive increase in noradrenaline (NA) turnover, increase baclofen analgesia by a clonidine-sensitive mechanism. Both ascending and descending NA pathways are implicated in the action of baclofen because dorsal bundle lesions, intrathecal 6-hydroxydopamine and medullary A1 lesions markedly decrease baclofen analgesia. However, simultaneous depletion of NA in ascending and descending pathways by locus coeruleus lesions potentiates baclofen analgesia suggesting a functionally important interaction between the two aspects. Baclofen analgesia within the spinal cord may be mediated by a distinct baclofen receptor because GABA does not mimic the effect of baclofen and the rank order of potency both of close structural analogs of baclofen as well as antagonists differs for analgesia and GABAB systems. The spinal mechanism may involve an interaction with substance P (SP) because SP blocks baclofen analgesia, and desensitization to SP alters the spinal analgesic effect of baclofen. GABA uptake inhibitors produce analgesia which is similar to that produced by GABAA agonists because it is blocked by atropine, scopolamine and yohimbine. Analgesia produced by GABA-transaminase inhibitors is similar to that produced by GABAA agonists because it can be blocked by atropine, but it is potentiated by haloperidol while THIP analgesia is not.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:GABAergic mechanisms of analgesia: an update. 303 1

Bicuculline methiodide, a GABAA antagonist produced potent analgesia in the tail pinch test when it was given intracisternally (i.c.) but not intrathecally (i.t.). The ED50 was 5 ng/mouse. This analgesia was antagonized by i.c. muscimol, a GABAA agonist. On the contrary, muscimol (i.t.) produced bicuculline-reversible analgesia. These findings suggest that brain GABA may transmit the nociceptive information while GABA in the spinal cord may inhibit it.
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PMID:Subconvulsive doses of intracisternal bicuculline methiodide, a GABAA receptor antagonist, produce potent analgesia as measured in the tail pinch test in mice. 303 41

The effects of intracerebroventricular (i.c.v.) administrations of the progesterone metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3A5P), on the nociceptive responses of male mice were examined. 3A5P elicited significant, dose-dependent (0.001-1.0 microgram) analgesia for 90-120 min after administration. These effects of 3A5P were significantly more potent than those of progesterone. The stereoisomer, 3 beta-hydroxy-5 alpha-pregnan-20 one (3B5P), failed to affect the nociceptive responses, indicating that the analgesic effect of 3A5P is stereospecific. The analgesic effects of 3A5P were blocked by peripheral administrations of the GABA antagonists, bicuculline and picrotoxin, and reduced by both the opiate and benzodiazepine antagonists, naloxone and Ro 15-788, respectively. The calcium channel antagonists, nifedipine and verapamil, enhanced 3A5P-induced analgesia but had no evident effects on the actions of 3B5P. These results suggest that the central analgesic effects of the progesterone metabolite, 3A5P, may arise via mechanisms involving calcium channels, the GABA-benzodiazepine-chloride complex and endogenous opioid systems.
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PMID:Analgesic effects of the progesterone metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-one, and possible modes of action in mice. 311 42

The effects of intracerebroventricular (i.c.v.) administrations of the putative follicle stimulating hormone (FSH) suppressing gonadal steroid, 3 alpha-hydroxy-4-pregnen-20-one (3A4P) on the nociceptive responses of male mice were examined. This allylic steroid elicited significant, dose-dependent (0.001-1.0 micrograms) analgesic responses for 90-150 min after injection. These analgesic effects of 3A4P were stereospecific, the stereoisomer, 3 beta-hydroxy-4-pregnen-20-one (3B4P) failing to affect the nociceptive responses. The analgesic effects of 3A4P were blocked by peripheral administrations of the GABA antagonists, bicuculline and picrotoxin, and reduced by the benzodiazepine antagonist, Ro 15-1788. The exogenous opiate antagonist, naloxone, and the putative endogenous opioid antagonist, Tyr-MIF-1 (Pro-Leu-Gly-amide), also reduced 3A4P-induced analgesia, while i.c.v. administration of 3A4P (0.001 and 0.01 micrograms) itself attenuated the analgesic effects arising from peripheral administrations of opiate receptor agonist, morphine. In addition, the calcium channel antagonists, nifedipine and verapamil, enhanced 3A4P-induced analgesia but had no evident effects on the actions of 3B4P. These results suggest that the central analgesic effects of the FSH-suppressing steroid, 3A4P, arise via benzodiazepine--GABA--opiate mechanisms and calcium channels. These findings also suggest possible central modes of action whereby 3A4P may elicit selective suppression of FSH.
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PMID:Analgesic effects of the putative FSH-suppressing gonadal steroid, 3 alpha-hydroxy-4-pregnen-20-one: possible modes of action. 314 22

The involvement of the GABA system in dopamine-acetylcholine interactions in electroacupuncture induced analgesia (EAA), measured in terms of tail flick latency (TFL) test, was studied with administration of the GABA receptor agonist, muscimol (1 mg/kg, i.p.); antagonist, bicuculline (2 mg/kg, i.p.); GABAmimetic drug, ethanolamine-O-sulfate (EOS) (2 mg/kg, s.c.) or the drugs stimulating or inhibiting acetylcholine and dopamine receptors activity to rats exposed to electroacupunture (EA). All the drugs were administered prior to EA (10 Hz, 1 volt) exposure (2-15 min). Results observed under the above conditions suggest that the cholinergic system has a direct inhibitory role on EAA and the dopaminergic system mediates its action via the cholinergic system. A decrease in EAA with both the GABA receptor agonist and antagonist and tremendous increase of EAA with the gabamimetic drug, EOS, showed that GABA receptors may not be directly involved in EAA. Further (a) gradual withdrawal of muscimol, bicuculline or physostigmine induced decrease in EAA with the increase in duration of EA exposure; (b) the characteristic changes in EAA observed with the coadministration of (i) L-DOPA + carbidopa + muscimol (ii) atropine + muscimol; and (c) no significant change in bicuculline + physostigmine induced inhibition of EAA with the increase in duration of EA exposure suggest that some inhibitory substance(s) may be released during EA which may inhibit the GABA system and finally cholinergic activity through the activation of dopaminergic neurone.
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PMID:Possible involvement of the GABAergic system in dopaminergic-cholinergic interactions in electroacupuncture-induced analgesia. 326 52

To elucidate the functional role of mesolimbocortical dopamine(DA)-containing and other mediator-specific neurons in mediation of different pharmacological effects of opiates, morphine (6 mg/kg, SC)-induced modification of spontaneous discharges of different types VTA-units and their changes during polymodal activating and aversive stimulation and spontaneous movement were studied in conscious, restrained rats. In presumed DA-containing neurons (D-type) prolonged increase of discharge rate, regularization of their pattern and decrease of firing changes during all types of external stimulation and spontaneous or stimulus-induced movement activity were found. This decrease of unit firing changes was connected with significant rising of atypical, compared with control conditions, firing inhibitions. Changes of presumed acetylcholine(ACh)-containing neurons (A-B type) properties were defined as prolonged and pronounced decrease of firing rate, intensification of bursting pattern and decrease of discharge changes during all types of stimulation used and animal movements. This decrease of discharge changes was associated with significant lowering of activations-typical for these units in control conscious animals and rising of firing inhibitions. In presumed ACh- or GABA-containing interneurons of C-type a significant decrease of firing rate, increase of activations and decrease of firing inhibitions, typical for these units in control conscious rats were found. The modifications of different VTA-unit functional properties are discussed in view of main pharmacological effects of opiates (sedation, analgesia, positive reinforcement, movement activation).
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PMID:Morphine-induced modification of the functional properties of ventral tegmental area neurons in conscious rat. 341 Jun 51

The novel neuropeptide, neo-kyotorphin, produced a naloxone-resistant analgesia in the tail pinch test when given (IC) to mice. Pretreatments with implantation of a morphine pellet or with phentolamine (10 micrograms IT) or with reserpine (10 mg/kg SC) did not attenuate this analgesia, yet the analgesia was antagonized by GABA mimetics, such as muscimol (0.1 microgram IC), nipecotic acid (100 mg/kg IP). Neo-kyotorphin inhibited the Ca2+-dependent and depolarization-evoked release of 3H-GABA, from crude synaptosomes of the lower brain stem of rats. These findings suggest that inhibition of GABA in the brain may in part be involved in neo-kyotorphin-induced analgesia.
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PMID:Non-opioid analgesia of the neuropeptide, neo-kyotorphin and possible mediation by inhibition of GABA release in the mouse brain. 343 36

Picrotoxin, an antagonist of GABA-associated chloride ionophores with convulsant activity, possesses antinociceptive activity in the hot-plate and writhing tests in the mouse. Analgesia produced by a subconvulsant dose of picrotoxin (0.75 mg/kg, s.c.) was reversed by naloxone (1.0 mg/kg, s.c.), atropine (5 mg/kg, i.p.), and methysergide (10 mg/kg, i.p.) in the jumping reaction (hot-plate test). These data indicate that opiate pathways, as well as cholinergic and serotoninergic pathways could be involved in the mechanism that underlies picrotoxin-induced analgesia. Furthermore, such results should be considered when interpreting the behavioral effects of picrotoxin.
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PMID:Antinociceptive action of picrotoxin in the mouse. 375 56


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