Dipyrone, a novel anticonvulsant agent? Insights from three experimental epilepsy models

Doretto, Maria Carolina; García-Cairasco, Norberto; Pimenta, N. J. G.; Souza, Danilo Almeida; Tatsuo, M.A.K.F.

doi:10.1097/00001756-199807130-00048

Cited by 28 publications

(23 citation statements)

References 6 publications

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“…Different hypotheses to explain this effect have been proposed, such as the inhibition of prostaglandin production, blockade of the inactivation of adenosine (a potent inhibitory neuromodulator), activation of GABA A receptors, and an antiglutamatergic effect (32,33). Finally, an extrasynaptic presence of GABA B receptors has been proposed, although for these receptors to be activated continuously, elevated concentrations of GABA in the extracellular fluid are necessary or its concentration needs to be increased close to these receptors through the release from various neurons (4,23,34).…”

Section: Discussionmentioning

confidence: 99%

Effect of the GABA B agonist baclofen on dipyrone-induced delayed gastric emptying in rats

Collares

Vinagre

2005

Braz J Med Biol Res

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Dipyrone administered intravenously (iv) or intracerebroventricularly (icv) delays gastric emptying (GE) in rats. Gamma-aminobutyric acid (GABA) is the most potent inhibitory neurotransmitter of the central nervous system. The objective of the present study was to determine the effect of icv baclofen, a GABA B receptor agonist, on delayed GE induced by dipyrone. Adult male Wistar rats received a saline test meal containing phenol red as a marker. GE was indirectly evaluated by determining the percent of gastric retention (%GR) of the meal 10 min after orogastric administration. In the first experiment, the animals were injected iv with vehicle (C iv ) or 80 mg/kg (240 µmol/kg) dipyrone (Dp iv ), followed by icv injection of 10 µl vehicle (bac0), or 0.5 (bac0.5), 1 (bac1) or 2 µg (bac2) baclofen. In the second experiment, the animals were injected icv with 5 µl vehicle (C icv ) or an equal volume of a solution containing 4 µmol (1333.2 µg) dipyrone (Dp icv ), followed by 5 µl vehicle (bac0) or 1 µg baclofen (bac1). GE was determined 10 min after icv injection. There was no significant difference between control animals from one experiment to another concerning GR values. Baclofen at the doses of 1 and 2 µg significantly reduced mean %GR induced by iv dipyrone (Dp iv bac1 = 35.9% and Dp iv bac2 = 26.9% vs Dp iv bac0 = 51.8%). Similarly, baclofen significantly reduced the effect of dipyrone injected icv (mean %GR: Dp icv bac1 = 30.4% vs Dp icv bac0 = 54.2%). The present results suggest that dipyrone induces delayed GE through a route in the central nervous system that is blocked by the activation of GABA B receptors. Correspondence

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Section: Discussionmentioning

confidence: 99%

Effect of the GABA B agonist baclofen on dipyrone-induced delayed gastric emptying in rats

Collares

Vinagre

2005

Braz J Med Biol Res

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“…We previously observed that dipyrone is also active against pentylenetetrazole seizures (Magalhaes LH, Doretto MC and Moraes MF, unpublished results). The dose of dipyrone used was that with a maximal effect and was obtained from a previously constructed dose-response curve (10).…”

Section: Discussionmentioning

confidence: 99%

“…For audiogenic seizures, genetically susceptible female animals (60-90 days old) were taken from our own colony of Wistar audiogenic rats, currently bred at the animal facilities of the Physiology and Biophysics Department at the Institute of Biological Sciences, Federal University of Minas Gerais, Brazil (10,13). In both groups, animals were housed 5 per cage and kept at 24ºC with free access to food and water under a 12-h artificial light/dark cycle.…”

Section: Animalsmentioning

confidence: 99%

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Do endogenous opioids and nitric oxide participate in the anticonvulsant action of dipyrone?

Reis

Doretto

Duarte

et al. 2003

Braz J Med Biol Res

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It was previously reported that systemic administration of dipyrone inhibited the tonic component of generalized tonic-clonic seizures in both the electroshock and the audiogenic seizure models. The aim of the present study was to investigate the mechanisms involved in the anticonvulsant action of dipyrone by assessing the role of nitric oxide and opioids in the electroshock (female 60-to 90-day-old Wistar rats, N = 5-11) and audiogenic seizure (female 60-to 90-day-old Wistar audiogenic rats, N = 5-11) models of epilepsy. Naloxone (5 mg/kg, sc) significantly reversed the anticonvulsant effect of dipyrone in rats submitted to the induction of audiogenic seizures (ANOVA/Bonferroni's test), suggesting the involvement of opioid peptides in this action. In the electroshock model no reversal of the anticonvulsant effect of dipyrone by naloxone (5 mg/kg, sc) was demonstrable. The acute (120 mg/kg, ip) and chronic (25 mg/kg, ip, twice a day/4 days) administration of L-NOARG did not reverse the anticonvulsant action of dipyrone in the audiogenic seizure model, suggesting that the nitric oxide pathway does not participate in such effect. Indomethacin (10, 20 and 30 mg/kg, ip) used for comparison had no anticonvulsant effect in the audiogenic seizure model. In conclusion, opioid peptides but not nitric oxide seem to be involved in the anticonvulsant action of dipyrone in audiogenic seizures. Correspondence

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“…Other central effects, distinct from this analgesic effect, have been evaluated. Dipyrone has been shown to produce anticonvulsant effect in rats exposed to the audiogenic and electroshock-induced seizures [7]. Dipyrone was also found to reverse the mechanical allodynia induced by CFA, and reduce the immobility time in tail suspension test in a study that compares the depression-like behavior of analgesics and bupropion in a model of chronic inflammation-related depression in mice [8].…”

mentioning

confidence: 97%

Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences

Kıroğlu¹,

Demirkol²,

Berktaş³

et al. 2016

CIM

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Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences Abstract Purpose: Antidepressant effects of analgesics have been investigate in both clinical and experimental studies. The purpose of this study was to investigate if the analgesic-antipyretic drug, dipyrone, also had antidepressant-like effects.Methods: Depression-like effects were investigated in an unpredictable chronic mild stress (UCMS) model in both male and female mice. Cage changes, light-dark cycle reversal, cage tilting, wet floor, empty cage, foreign material on the floor and predator sounds were used to induce light stress at different times for six weeks. Dipyrone was administered intraperitoneally beginning from the third week. Splash, rota-rod (RR) and forced swimming (FST) tests were performed at the seventh week as behavioural tests to evaluate the antidepressant-like effects of dipyrone. Coat state score (CSS) and weights of animals were recorded at seventh weeks. Results were analyzed using one or two-way ANOVA followed by the Bonferonni post hoc test.Results: Weight of UCMS-exposed mice did not change compared with controls; however, significant changes were observed in CSS in both sexes of stressed mice (p<0.05). RR latency decreased and immobility time enhanced in FST test in both sexes of stressed mice (p<0.05). Grooming behaviour was not different between the groups in female mice, but different in male mice in the splash test. Dipyrone did not produce a significant change in CSS in the UCMS-exposed group but reversed the latency time and immobility time to normal values in both sexes of mice and augmented the number of grooming behaviour only in stressed male mice. Conclusion:These results indicate that dipyrone produce antidepressant-like effects to some symptoms of UCMS according to gender.SUPPLEMENT

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Dipyrone, a novel anticonvulsant agent? Insights from three experimental epilepsy models

Cited by 28 publications

References 6 publications

Effect of the GABA B agonist baclofen on dipyrone-induced delayed gastric emptying in rats

Effect of the GABA B agonist baclofen on dipyrone-induced delayed gastric emptying in rats

Do endogenous opioids and nitric oxide participate in the anticonvulsant action of dipyrone?

Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences

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