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Biomedical subjects

Z Kleinrok

Publications and source records attributed to Z Kleinrok.

At least 163 records · Page 9Linked to original sources
PubMed1988

Dopamine-sensitive anticonvulsant site in the rat striatum.

The basal ganglia are involved in the organization of movement and function in the initiation and expression of generalized and limbic seizures. Dopamine is the principal neurotransmitter of the mesencephalic efferent pathways terminating in the mammalian striatum. No function has been ascribed to mesostriatal dopamine in the control of seizure spread in the brain. This work presents evidence that bilateral application of picomole amounts of apomorphine (a dopamine agonist) into the striatum confers protection against seizures produced by pilocarpine (a cholinergic agonist) in rats. The anticonvulsant effect of apomorphine is topographically confined to the caudate-putamen, nucleus accumbens, and olfactory tubercle. Bilateral application of nanomolar amounts of haloperidol (a dopamine antagonist) into the caudate-putamen or systemic application of haloperidol both lower the threshold for pilocarpine-induced seizures. Local application of an excitatory amino acid N-methyl-D-aspartate, into the substantia nigra pars compacta, ventral tegmental area, or retrorubral area, sites of origin of mesostriatal dopaminergic pathways, protects rats against seizures produced by pilocarpine. These results suggest that dopaminergic transmission in the striatum may be operative in complex neuronal networks modulating the seizure threshold.

Amino Acids↗
PubMed1987

Inhibition of aminophylline-induced convulsions in mice by antiepileptic drugs and other agents.

Common antiepileptic drugs and agents affecting different neurotransmitter systems were studied against aminophylline (280 mg/kg i.p.)-induced convulsions in mice. All drugs and agents were administered i.p. Diazepam and phenobarbital antagonized the whole seizure pattern and the respective ED50 values for the clonic phase were 3.5 and 62 mg/kg. Valproate at 500 mg/kg protected fewer than 50% of mice against the clonic phase. The remaining antiepileptics (acetazolamide, up to 1,000 mg/kg; carbamazepine and diphenylhydantoin, up to 50 mg/kg; ethosuximide, 500 mg/kg and trimethadione, 400 mg/kg) were totally ineffective in this respect. Propranolol (up to 20 mg/kg), baclofen (20 mg/kg), gamma-hydroxybutyric acid (300 mg/kg), aminooxyacetic acid (20 mg/kg), clonidine (up to 0.2 mg/kg), ketamine (30 mg/kg), atropine (20 mg/kg), papaverine (50 mg/kg) and L-phenylisopropyladenosine (2 mg/kg) did not affect the clonic phase either. Only antagonists of N-methyl-D-aspartic acid excitation, 2-amino-5-phosphonopentanoic acid and 2-amino-7-phosphonoheptanoic acid afforded protection against aminophylline-induced clonic seizure activity. The results show that aminophylline convulsions are relatively resistant to antiepileptic drugs and suggest that antagonists of excitatory transmission are potential antiaminophylline drugs.

2-Amino-5-phosphonovalerate↗
PubMed1986

Comparison of subacute toxicity of rubidomycine and its four derivatives.

In experiments carried out on Albino-Swiss mice we tried to compare some pharmacological properties of standard compound-rubidomycin with its 4 newly synthetized derivatives. DR-16 appeared to be more toxic compound than rubidomycin and DR-19 was found to possess the lowest toxicity.

Alanine Transaminase↗
PubMed1986

comparison of pharmacological properties of cyclophosphamide and its enantiomers.

Comparison of pharmacological properties of commercial racemic Cyclophosphamide and its D- and L-enantiomers was performed in experiments on mice and rats. Acute toxicity, behavioral screening tests and the effects of subchronic treatment (influence on body mass, the increase of the mass of internal organs, mortality, morphology of peripheral blood, biochemical investigations of blood plasma, microscopic evaluation of liver and bladder) were taken into account. Summarized results revealed the most pronounced toxicity of D-cyclophosphamide. L-enantiomer was more toxic when compared with racemate. As several reports in literature confirmed the greatest antineoplastic activity of L-form in animals, the suggestion of further clinical investigation of levorotatory form as a separate preparation has been put forward.

Animals↗
PubMed1986

Pharmacological evaluation of ifosfamide and its enantiomers in laboratory animals.

Some pharmacological properties of commercial racemic ifosfamide (Holoxan) and its D- and L-enantiomers were compared in experiments on mice and rats. Although values of acute toxicity and some results of subchronic treatment revealed better parameters of L-form in comparison to racemic mixture, distinct hepatotoxic effects and thrombocytopenia noted in the course of prolonged treatment seem to be the important factors limiting therapeutic usefulness of levorotatory form.

Animals↗
PubMed1986

Comparison of selected pharmacological properties of trofosfamide and its enantiomeric derivatives.

Comparison of pharmacological properties of commercial, racemic trofosfamide (Ixoten) and its dextrorotatory and levorotatory derivatives was performed in experiments on mice. Acute and cumulative toxicity, behavioral screening tests and effects of subchronic treatment (growth of body mass, mortality, blood morphology, proteins level, enzymes activity, microscopic evaluation of liver slices) were taken into account. Summarized data revealed more pronounced toxicity of enantiomers, particularly D-form, as compared with racemate.

Animals↗
PubMed1985

The effect of stimulation and blocking of histamine H2 receptors on the turnover of the serotonin in different parts of the alimentary tract and the brain of the rat.

In the experiments performed on Wistar rats it was found that histamine (0.05 and 0.5 mg/kg i.p.) caused an acceleration of the turnover of serotonin (5-HT) in the stomach. After the lowest dose of ranitidine (3 mg/kg i.p.) a decrease in the rate of 5-HT turnover in the stomach was observed, whereas the higher doses (15.0 and 30 mg/kg i.p.) accelerated the turnover of this amine. In the duodenum, both doses of histamine accelerated the turnover of 5-HT, however, ranitidine in all doses induced a reduction in the rate of 5-HT turnover in this part of the alimentary tract. In the intestine, both doses of histamine enhanced the turnover of 5-HT but after all doses of ranitidine a decrease of the turnover was observed. The blockade of histamine H2 receptors with ranitidine did not completely abolish the effects of histamine on the 5-HT system, in the parts of the rat digestive system studied which suggests also an indirect activity of other receptors in presented observations. In the rat brain, an acceleration of the turnover of 5-HT after both doses of histamine was found. However, ranitidine only reduced the rate of 5-HT turnover at the lowest dose. In animals treated with ranitidine (15 mg/kg i.p.) for three days, histamine did not produce any change in the turnover of 5-HT in rat brain. These experiments show, that in the alimentary tract a relationship exists between histaminergic and serotoninergic systems.

Animals↗
PubMed1985

Modification of the anticonvulsant activity of 2-amino-5-phosphonovalerate by agents affecting different neurotransmitter systems.

The effects of atropine (5 mg/kg), baclofen (10 mg/kg), gamma-hydroxybutyrate (300 mg/kg), gamma-butyrolactone (100 mg/kg) and muscimol (1 mg/kg) upon the action of 2-amino-5-phosphonovalerate (APV; an antagonist at receptors for N-methyl-D-aspartate) on the threshold current for seizures induced by electroshock, were studied in mice. Neither APV, up to 100 mg/kg, nor the other agents produced any significant increase in the convulsive threshold when tested alone. Muscimol had no effect on the action of APV (50 and 100 mg/kg) and the combination of APV with the subthreshold doses of atropine, baclofen, gamma-hydroxybutyrate and gamma-butyrolactone resulted in a clearcut anticonvulsant action. The observed increases in the threshold may be due to the suppressant effects of the drugs upon excitatory transmission, which eventually leads to the potentiation of the action of APV, resulting from blockade of N-methyl-D-aspartate receptors.

2-Amino-5-phosphonovalerate↗
PubMed1985

Effects of morphine and naloxone on pilocarpine-induced convulsions in rats.

Systemic administration of morphine hydrochloride (MF; 5-80 mg/kg; i.p.) in rats enhanced the epileptogenic potential of pilocarpine hydrochloride (PIL) in a dose-dependent manner. PIL, 100 mg/kg; i.p., which did not result in convulsions by itself, produced sustained limbic seizures and epileptic brain damage in MF-pretreated rats. MF-induced enhancement of PIL neurotoxicity was blocked by naloxone hydrochloride (NAL; 2 and 10 mg/kg; i.p.). Administration of NAL (2-20 mg/kg) prior to PIL in the dose of 380 mg/kg moderately decreased the incidence of convulsions, brain damage and lethal toxicity produced by this agent. These results support the hypothesis that opiate mechanisms are involved in the maintenance of the threshold for propagation of seizure activity within limbic circuits.

Animals↗
PubMed1985

Phosphonic analogues of excitatory amino acids raise the threshold for maximal electroconvulsions in mice.

2-Amino-5-phosphonopentanoic acid (100 and 200 mg/kg) and 2-amino-7-phosphonoheptanoic acid (50-200 mg/kg i.p.) significantly elevated the threshold for maximal electroconvulsions in mice, the latter being more effective in this respect. In contrast, neither alpha-aminoadipic acid nor L-glutamic acid diethyl ester (up to 200 and 400 mg/kg, respectively) offered any protection. The present results add further evidence to support the importance of the blockade of N-methyl-D-aspartic acid receptor-mediated events in the suppression of seizure activity.

2-Amino-5-phosphonovalerate↗