Influence of 5-(3-chlorophenyl)-4-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione on the anticonvulsant action of 4 classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 4
Abstract
Background: The aim of this study was to determine the effects of 5-(3-chlorophenyl)-4-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (TP10) on the protective action of 4 classical antiepileptic drugs - carbamazepine, phenobarbital, phenytoin and valproate - against maximal electroshock-induced seizures in mice. Methods: Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by an electric current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse-effect profiles with respect to motor performance, long-term memory and skeletal muscular strength were measured, together with total brain antiepileptic drug concentrations. Results: TP10 administered intraperitoneally at 10 mg/kg significantly elevated the threshold for electroconvulsions in mice. TP10 at doses of 2.5 and 5 mg/kg had no impact on the threshold for electroconvulsions in mice. Moreover, TP10 (5 mg/kg) significantly enhanced the anticonvulsant activity of valproate, but not that of carbamazepine, phenobarbital or phenytoin in the maximal electroshock seizure test in mice. Pharmacokinetic experiments revealed that TP10 significantly elevated total brain concentrations of valproate in mice. Conclusions: The enhanced anticonvulsant action of valproate by TP10 in the mouse maximal electroshock-induced seizure model was associated with a pharmacokinetic increase in total brain valproate concentrations in mice. The combinations of TP10 with carbamazepine, phenobarbital and phenytoin were neutral from a preclinical viewpoint.
Authors and Affiliations
Jarogniew Łuszczki, Tomasz Plech, Monika Wujec
Keywords
Related Articles
- EP ID EP119820
- DOI -
- Views 88
- Downloads 0
Inhibitory effect of antidepressants on B16F10 melanoma tumor growth.
Background: Antidepressant drugs, like fluoxetine, a selective serotonin reuptake inhibitor, desipramine, a nonselective noradrenaline reuptake inhibitor, and mirtazapine, an antagonist of noradrenaline α2 auto- and hete...
Antidepressant-like activity of the phenylpiperazine pyrrolidin-2-one derivatives in mice.
The present study was designed to investigate the central nervous system activity of 23 novel phenylpiperazine pyrrolidin-2-one derivatives. These compounds had marked antiarrhythmic and hypotensive activities and reveal...
Different effects of nitric oxide synthase inhibitors on convulsions induced by nicotine in mice.
Acute intraperitoneal (ip) administration of N(G)-nitro-L-arginine (NNA, 10, 20 and 40 mg/kg), a non-selective nitric oxide synthase (NOS) inhibitor, significantly and dose-dependently decreased the incidence of convulsi...
Partial lesion of the dopaminergic innervation of the ventral striatum induces "depressive-like" behavior of rats.
Depression is a frequent comorbid disorder in Parkinson's disease (PD) which may precede appearance of its motor symptoms by several years. Pathomechanisms underlying PD have been suggested to be responsible for the PD-r...
Physiology and pharmacology of melatonin in relation to biological rhythms.
Melatonin is an evolutionarily conserved molecule that serves a time-keeping function in various species. In vertebrates, melatonin is produced predominantly by the pineal gland with a marked circadian rhythm that is gov...