L-histidine is a beneficial adjuvant for antiepileptic drugs against maximal electroshock-induced seizures in mice.

Endogenous histamine has been reported to be involved in regulation of seizure susceptibility. Enhancement of histamine neurotransmission engendered by L-histidine treatment produces anticonvulsant effects in experimental animals. The present study investigated the influence of L-histidine on the protective effects of carbamazepine and phenytoin against maximal electroshock-induced seizures in mice.

Influence of sexual hormone antagonists on the anticonvulsant action of conventional antiepileptic drugs against electrically- and pentylenetetrazol-induced seizures in mice.

The present results refer to the action of three gonadal steroid antihormones, tamoxifen (TXF, an estrogen antagonist), cyproterone acetate (CYP, an antiandrogen) and mifepristone (MIF, a progesterone antagonist) on seizure phenomena in mice. TXF and CYP at their lowest protective dose in the electroconvulsive threshold test, enhanced the antiseizure efficacy of some antiepileptic drugs. TXF (20 mg/kg) potentiated the protective activity of valproate, diphenylhydantoin and clonazepam, but not that of carbamazepine or phenobarbital, against maximal electroshock-induced convulsions in female mice.

The influence of interferon alpha on the rat liver injured by chronic administration of carbon tetrachloride.

Due to their complex and not fully known etiopathogenesis as well as difficulties in treatment, chronic hepatitis and cirrhosis still remain one of the main problems of hepatologists. Nowadays, the use of IFN alpha is considered the most effective method of treatment in chronic hepatitis. Recently, a new property of IFN, i.

Influence of sex hormone antagonists on the anticonvulsant action of conventional antiepileptic drugs against amygdala-kindled seizures in male and female rats.

The effects of three gonadal steroid antihormones, tamoxifen (TXF, an estrogen antagonist), cyproterone acetate (CYP, an antiandrogen) and mifepristone (MIF, a progesterone antagonist) alone or combined with conventional antiepileptics were evaluated in amygdala-kindled seizures in male and female rats. None of the three antihormones used in this study affected any seizure parameter. TXF (50 mg/kg) and CYP (50 mg/kg), when combined with carbamazepine, or phenobarbital applied at their subprotective doses of 15 mg/kg, resulted in significant reductions of the seizure and afterdischarge durations, both in male and female rats.

Influence of LY 300164, an AMPA/kainate receptor antagonist upon the anticonvulsant action of antiepileptic drugs against aminophylline-induced seizures in mice.

LY 300164 [7-acetyl-3-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxazolo[4,5-h][2,3]-benzodiazepine], a novel AMPA/kainate receptor antagonist, administered intraperitoneally protected mice against aminophylline-induced seizures. At doses up to 0.5 mg/kg, which did not significantly affect the convulsant activity of aminophylline, it potentiated the protective activity of diazepam.

Synthesis and properties of tetra(hexa)hydropyrazolo [1,2-a]pyrido[3,4-d]pyridazine derivatives.

The synthesis of tetra(hexa)hydropyrazolo[1,2-a]pyrido[3,4-d]pyridazine derivatives (14-21) and the results of pharmacological screening are described in this paper. All compounds tested were non-toxic and showed a significant analgesic action. The analgesic effects were associated with the suppression of the spontaneous locomotor activity.

Excitatory amino acids in epilepsy.

Epilepsy has been described as a neurological disorder with a prevalence rate estimated at approximately 0.5% of population. In recent years there have been significant advances in our understanding of the contribution of excitatory glutamatergic transmission to seizures.

Investigations on the synthesis and pharmacological properties of 4-alkoxy-2-[2-hydroxy-3-(4-aryl-1-piperazinyl)propyl]-6-methyl-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones.

Synthesis of 2-[2-hydroxy-3-(4-aryl-1-piperazinyl)propyl] derivatives of 4-alkoxy-6-methyl-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones (8-12) is described. The chlorides used in the above synthesis can exist in two isomeric forms: chain (18-20) and cyclic (19a, 20a). The compounds 8-12 exhibited potent analgesic activity which was superior than that of acetylsalicylic acid in two different tests.

Interaction of the neurosteroid alphaxalone with conventional antiepileptic drugs in different types of experimental seizures.

A number of neurosteroids exert antiseizure and/or neuroprotective properties. The aim of this study was to evaluate the effect of the neurosteroid alphaxalone on the protective action of conventional antiepileptics in four seizure tests. Alphaxalone (up to 5 mg/kg) did not exert a significant action against amygdala-kindled seizures in rats, or against pentetrazole- or aminophylline-induced convulsions in mice.

Endothelium-dependent production and liberation of kynurenic acid by rat aortic rings exposed to L-kynurenine.

Rat aortic slices produced and liberated the endogenous antagonist of glutamate receptors, kynurenic acid, upon exposure to L-kynurenine. Endothelium-denuded slices did not synthesize any measurable amount of kynurenic acid, indicating its endothelial origin. Aortic kynurenic acid production was diminished by modification of the ionic milieu, hypoxia and hypoglycemia, as well as by L-glutamate and L-aspartate, endogenous glutamate receptor agonists, and aminooxyacetic acid, a non-selective inhibitor of aminotransferases and mitochondrial respiration.

Effects of tamoxifen, mifepristone and cyproterone on the electroconvulsive threshold and pentetrazole-induced convulsions in mice.

The aim of this study was to evaluate the efficacy of three antihormones, tamoxifen (TXF, an antiestrogen), mifepristone (MIF, an antiprogesterone) and cyproterone (CYP, an antiandrogen) in two major models of experimental epilepsy, electrically and pentetrazole (PTZ)-evoked seizures in mice. TXF (20-50 mg/kg) significantly raised the threshold for electroconvulsions in female mice, whereas CYP was active in male mice. Similar effects were observed in castrated mice.

Molsidomine potentiates the protective activity of GYKI 52466, a non-NMDA antagonist, MK-801, a non-competitive NMDA antagonist, and riluzole against electroconvulsions in mice.

The influence of molsidomine, a donor of nitric oxide (NO), L-arginine, a substrate for NO synthesis, and N(G)-nitro-L-arginine (NNA), an inhibitor of NO synthase, on the protective activity of CGP 40116, GYKI 52466, MK-801, and riluzole against electroconvulsions was studied in mice. Molsidomine (100 mg kg(-1); i.p.

Influence of agents affecting voltage-dependent calcium channels and dantrolene on the anticonvulsant action of the AMPA/kainate receptor antagonist LY 300164 in mice.

It was previously documented that calcium (Ca(2+)) channel inhibitors intensified the protective effects of conventional antiepileptics against electroconvulsions in mice. The aim of this study was to evaluate the effects of Ca(2+) channel inhibitors (nifedipine, nicardipine and flunarizine) on the anticonvulsant action of the new AMPA/kainate receptor antagonist, 7-acetyl-3-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxazolo[4,5-h][2,3]-benzodiazepine (LY 300164), against maximal electroshock (MES)-induced seizures in mice. Dantrolene (an inhibitor of Ca(2+)release from intracellular stores) was also included.

Niguldipine impairs the protective activity of carbamazepine and phenobarbital in amygdala-kindled seizures in rats.

There is evidence that some calcium (Ca(2+)) channel inhibitors enhance the protective activity of antiepileptic drugs. Since clinical trials have not provided consistent data on this issue, the objective of this study was to evaluate the interaction of a dihydropyridine, niguldipine, with conventional antiepileptics in amygdala-kindled rats. Niguldipine (at 7.

The influence of nifedipine (calcium channel blocker) and Bay-K-8644 (calcium channel agonist) on the development of experimental acute pancreatitis.

The aim of this paper was to evaluate the influence of nifedipine (calcium channel blocker) and Bay-K-8644 (calcium channel agonist) on cerulein acute pancreatitis (AP) in rats. AP was induced according to the Lampel and Kern method (1) by the continuous intravenous infusion of cerulein in the doses of 5 x 10(-6) g/kg/h for 12 hours. There was obtained a statistically significant decrease in serum amylase activity and pancreatic weight in the groups treated with higher doses of nifedipine before infusion of the cerulein compared with rats treated only with cerulein.

Molsidomine enhances the protective activity of valproate against pentylenetetrazole-induced seizures in mice.

Molsidomine (25 mg kg(-1)), a donor of nitric oxide, commonly used in the treatment of coronary artery disease, enhanced the protective activity of valproate against the clonic phase of pentylenetetrazole-induced seizures in mice, significantly reducing the ED(50) of valproate from 123.5 to 78 mg kg(-1). Molsidomine was found to be ineffective with respect to the protective action of clonazepam, ethosuximide and phenobarbital.

Effect of diazepam and clonazepam on the function of isolated rat platelet and neutrophil.

Background: Benzodiazepine binding sites distinct from the GABA-receptor-chloride-complex in the central nervous system have been recognized in many peripheral tissues, but their physiological role remains unexplained. Our study was undertaken to examine the effects of diazepam, clonazepam, and PK 11195, a peripheral benzodiazepine receptor antagonist, on the functional and biochemical responses of platelets and neutrophils stimulated by different physiological agonists.

Material/methods: The experiments were conducted on isolated washed rat platelets activated by arachidonic acid (AA), adenosine 5'-diphosphate (ADP), or thrombin and on isolated rat neutrophils activated by a chemotactic peptide, formyl methionyl leucyl phenylalanine (fMLP).

Evaluation of toxic activity of 2,4-dihydroxythiobenzanilides.

2,4-Dihydroxythiobenzanilides represent a new group of compounds with significant fungistatic and bacteriostatic properties. The results of investigations on their cytotoxicity are also very convincing. Therefore LD50 doses were determined for five compounds, they ranged from 239 to 840.

Nitric oxide and convulsions in 4-aminopyridine-treated mice.

We studied whether N(G)-nitro-L-arginine (NNA), an inhibitor of nitric oxide (NO) synthase as well as L-arginine and molsidomine, two agents elevating NO, influenced convulsions caused by 4-aminopyridine, a K+ channel blocker in mice. NNA, in a dose known to decrease level of NO (40 mg x kg(-1)), enhanced the seizure susceptibility to intraperitoneal (i.p.

Synthesis and in vivo pharmacology of new derivatives of isothiazolo[5,4-b]pyridine of Mannich base type.

Recently we reported on 2H-4,6-dimethyl-2-[(4-phenylpiperazin-1-yl)methyl]-3-oxo-2,3-dihydroisothiazolo[5,4-b]pyridine (V), which exhibited high anorectic action in animal models as a result of stimulation of serotoninergic system. This paper describes the synthesis of the series 3-5 of analogues of V prepared from 2-hydroxymethyl-4,6-dimethylisothiazolopyridine (2) and corresponding 4-substituted-piperazines(piperidines) or tetrahydroisoquinoline. The 12 compounds obtained were screened in standard CNS tests in in vivo (mice and rats).

Propranolol and metoprolol enhance the anticonvulsant action of valproate and diazepam against maximal electroshock.

The anticonvulsive potential of classical antiepileptics co-administered with beta-adrenergic receptor antagonists against generalized tonic-clonic seizures was evaluated in the model of maximal electroshock (MES)-induced convulsions. Propranolol, acebutolol, metoprolol and atenolol were tested in the doses not affecting the electroconvulsive threshold. Propranolol and metoprolol lowered the ED(50) of valproate and diazepam.

Interaction of GYKI 52466, a selective non-competitive antagonist of AMPA/kainate receptors, with conventional antiepileptic drugs in amygdala-kindled seizures in rats.

GYKI 52466 [1,4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine], a non-competitive AMPA/kainate receptor antagonist, administered i.p. at the dose of 5 mg/kg, exerted a significant anticonvulsant effect, as it decreased seizure and afterdischarge durations, being ineffective at 2 mg/kg.

Effect of adenosine A1 and A2 receptor stimulation on hypoxia-induced convulsions in adult mice.

Clinical observations indicate that seizures induced by hypoxia are common kind of convulsive activity in both infants and elderly patients. The occurrence of seizure episode during hypoxia is important risk factor of epilepsy development in the future. Experimental hypoxia was obtained by exposure of adult (20-23 g) Albino Swiss mice to spontaneous breathing in gas mixture composed of 5% oxygen and 95% nitrogen.

beta-Adrenoceptor blockade enhances the anticonvulsant effect of glutamate receptor antagonists against maximal electroshock.

In this study, we evaluated whether beta-adrenoceptor antagonists may modify the protective efficacy of dizocilpine (MK-801), a NMDA receptor antagonist, and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), a non-NMDA (AMPA/kainate) receptor antagonist, against maximal electroshock-induced seizures in mice. Propranolol, acebutolol, metoprolol and atenolol were used in doses that did not alter the electroconvulsive threshold. Propranolol potentiated the anticonvulsant activity of MK-801 and GYKI 52466, significantly lowering their ED(50) values from 0.

Influence of D(-)CPP and (+/-)CPP upon the protective action of conventional antiepileptic drugs against electroconvulsions in mice.

Competitive antagonists of N-methyl-D-aspartate (NMDA) receptors, D(-) CPP (up to 0.625 mg/kg) and (+/-)CPP (up to 0.625 mg/kg), did not influence the electroconvulsive threshold in mice.