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Biomedical subjects

Z Kleinrok

Publications and source records attributed to Z Kleinrok.

At least 127 records · Page 7Linked to original sources
PubMed1994

Central action of glaucine in rodents.

It was found that glaucine (7, 14 and 28 mg/kg ip) decreased locomotor activity, did not affect the body temperature and potentiated the amphetamine and apomorphine stereotypy but did not affect the amphetamine hypermotility. Besides, glaucine antagonized haloperidol-induced catalepsy of the rats. Glaucine was without analgesic, anticonvulsant, antianxiety and antidepressive effects in mice. This alkaloid in doses of 14 and 28mg/kg ip antagonized the head twitch response induced by 5-HTP in the rats. Further, glaucine decreased the hyperthermia induced by m-CPP in rats kept at high ambient temperature. It was found that glaucine depressed the noradrenaline (NA) and dopamine (DA) levels in the whole brain of mice. Besides, this alkaloid significantly decreased the brain level of 5-hydroxytryptamine (5-HT), without changing the 5-hydroxyindoleacetic acid (5-HIAA) concentration.

Animals↗
PubMed1994

Acute and chronic toxicity of "Polfa" perphenazine.

The toxicity of "Polfa" perphenazine and its profile of pharmacological properties were estimated. LD50 values calculated in rats were 2000 mg/kg and 325 mg/kg, after p.o. and i.p. administration respectively. Chronic toxicity of the perphenazine was evaluated during the period of 3 month of the drug treatment p.o. or i.p. in the rats and mice. Decrease of the locomotor activity of perphenazine was observed after the highest dose (15 mg/kg) of the drug, only in the first weeks of the experiment. Also the cataleptogenic effect of perphenazine observed in the mice was diminished during 3 month of the experiment. Moreover, perphenazine did not induced significant changes in the blood morphology and histology of the internal organs.

Animals↗
PubMed1994

Studies on synthesis and biological properties of pyrazolo[4,3-c]-pyrido[3,2-e]-1,2-thiazine-5,5-dioxide bearing 4-substituted-1-piperazinylpropyl moiety.

Derivatives of the pyrazolopyridothiazine-5,5-dioxide 6 and the pyridothiazine-1,1-dioxide 2 bearing 4-phenyl-(heteroaryl)-1-piperazinylpropyl substituent at the nitrogen of the thiazine ring were synthesized. The acute toxicity and preliminary results of the CNS activity of some derivatives 2 and 6 are described. A structure-activity relationship is discussed.

Animals↗
PubMed1994

[Androgens and the brain].

Recent years investigations provided, that androgens belong to the group of neurosteroids synthetized and metabolized in the brain tissue by both: the cells (neurons and glia) and the white matter. Two basal metabolic pathways of androgens: aromatisation and 5-alpha-reduction probably serve different physiological functions in different life periods. During the fetal life are the crucial processes for the organisation of the brain centers toward male patterns. At latter stages might play an important role in the feedback mechanisms controlling LH secretion. The action of neurosteroids is mediated by classic nuclear receptors, but also by cell-membrane receptors, and this effect is rapid and specific. Androgens can also modulate the action of others neurotransmitters by binding to their cell-membrane receptors, eg. GABA-A.

Androgens↗
PubMed1994

The effect of recombinant human erythropoietin (r-Hu EPO) administration on the blood chemistries and composition in uremic rats.

Recombinant human erythropoietin (r-Hu EPO) therapy improves the anaemia of patients on chronic hemodialysis, on peritoneal dialysis and those with chronic renal failure who have not yet started any form of renal replacement therapy. In the last category there is concern that r-Hu EPO therapy may be associated with deterioration of the reserve renal function. But new data showed that even during more prolonged treatment the correction of anaemia does not have a major detrimental effect on renal function. The study was undertaken to examine the influence of r-Hu EPO therapy on renal function and rheological erythrocytes finding in uremic rats.

Animals↗
PubMed1994

Pharmacological properties of racemic chlorobromofosfamide.

Racemic chlorobromofosfamide (CBM-4A) is a bromine substituted analog of ifosfamide. The studies reported here were aimed at establishing the general pharmacological properties and toxicologic profile of this compound. Acute and cumulative toxicity, behavioral screening tests and effects of subchronic and chronic treatment (influence on body weight, mortality, blood morphology, proteins level, urea and creatinine concentration, enzymes activity) were taken into account. Summarized data revealed that CBM-4A possessed similar properties as other oxazaphosphorine cytostatics.

Animals↗
PubMed1993

Competitive NMDA receptor antagonists enhance the antielectroshock activity of various antiepileptics.

CGP 37849 (1 mg/kg i.p.) enhanced the protective action of carbamazepine, diphenylhydantoin and phenobarbital against maximal electroshock-induced convulsions in mice. At 0.25 mg/kg CGP 37849 was inactive and at 0.5 mg/kg it potentiated the anticonvulsive activity of phenobarbital. CGP 39551 (5 mg/kg i.p.) reduced the ED50 values of diphenylhydantoin and phenobarbital, being without influence on carbamazepine. In the dose of 1.25 mg/kg, CGP 39551 potentiated the antielectroshock action of diphenylhydantoin and at 2.5 mg/kg that of phenobarbital. Neither NMDA receptor antagonist elevated the total plasma levels of antiepileptic drugs. Consequently, a pharmacokinetic interaction (in terms of total plasma levels at least) seems unlikely to be responsible for the observed potentiation of the antiepileptic drugs' activity. Combinations of CGP 37849 with either carbamazepine or phenobarbital resulted in a motor and memory impairment quantified by the chimney test and passive avoidance task, respectively. Moreover, combined treatment with phenobarbital and CGP 39551 caused a memory deficit. In contrast, diphenylhydantoin combined with either CGP 37849 or 39551 was devoid of adverse effects. It may be concluded that NMDA receptor blockade results in enhanced anticonvulsive action of common antiepileptics against maximal electroshock-induced seizures.

2-Amino-5-phosphonovalerate↗
PubMed1993

Competitive antagonists of NMDA receptors, CGP 37849 and CGP 39551, enhance the anticonvulsant activity of valproate against electroconvulsions in mice.

Two novel N-methyl-D-aspartic acid (NMDA) competitive antagonists, CGP 37849 (1.25 and 2.5 mg/kg) and CGP 39551 (10 mg/kg), significantly raised the threshold for electroconvulsions in mice. CGP 37849 in doses of 0.125-1.0 mg/kg and CGP 39551 in doses of 0.625-5 mg/kg i.p. considerably potentiated the protective activity of magnesium valproate against maximal electroshock-induced convulsions. The anticonvulsant activity of sodium valproate was potentiated by CGP 37849 (1 mg/kg) to a similar degree, which suggests that magnesium is not involved in the observed interaction. Neither CGP agent influenced the plasma level of valproate, so a pharmacokinetic interaction, in terms of total plasma levels, is not probable. Furthermore, the performance of mice injected with magnesium valproate (91 mg/kg) and CGP 37849 (0.25 mg/kg), which provided 50% protection against maximal electroshock-induced convulsions, in the long-term memory test and chimney test did not differ significantly from that of the control animals. The combination of magnesium valproate and CGP 39551 had a neurotoxic potential comparable to that of valproate alone. The results suggest that a combined treatment of valproate and some competitive NMDA antagonists may be important from a clinical point of view.

2-Amino-5-phosphonovalerate↗
PubMed1993

Influence of aminophylline and 8-(p-sulfophenyl)theophylline on the anticonvulsive action of diphenylhydantoin, phenobarbital, and valproate against maximal electroshock-induced convulsions in mice.

Aminophylline (theophylline2.ethylenediamine) in the dose of 12.5 mg/kg (i.p.) was ineffective upon all antiepileptic drugs studied and at the higher dose of 25 mg/kg, impaired the anticonvulsant action of phenobarbital and valproate against maximal electroshock in mice. The protection offered by diphenylhydantoin was diminished by aminophylline at 50 mg/kg (0.238 mmol of anhydrous theophylline/kg). In contrast, 8-(p-sulfophenyl)theophylline (a theophylline derivative unable to cross the blood-brain barrier) in the dose of 80 mg/kg (0.238 mmol/kg) did not influence the protective activity of diphenylhydantoin, phenobarbital, and valproate. It might be concluded that the aminophylline-induced impairment of the anticonvulsant action of common antiepileptic drugs results from the central effects of this methylxanthine.

Aminophylline↗
PubMed1993

2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline enhances the protective activity of common antiepileptic drugs against maximal electroshock-induced seizures in mice.

NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline), a novel and selective AMPA antagonist, was tested to evaluate its influence upon anticonvulsant activity of common antiepileptic drugs in mice. NBQX (10, 20, 40 mg/kg, i.p.) had no influence upon the threshold for electroconvulsions. NBQX (10 mg/kg) enhanced the activity of anticonvulsant drugs decreasing their ED50S against maximal electroshock from 321 to 190 mg/kg for valproate, from 19.5 to 14.5 mg/kg for carbamazepine, from 31.0 to 21.4 mg/kg for phenobarbital, from 17.8 to 9.5 mg/kg for diphenylhydantoin and from 19.5 to 10.5 mg/kg for diazepam. In addition, NBQX (10 mg/kg) failed to impair motor performance and long-term memory determined in the chimney test and passive avoidance task. The combinations of NBQX (10 mg/kg) and carbamazepine, diphenylhydantoin or phenobarbital resulted in no adverse effects. Diazepam (10.5 mg/kg) alone impaired the motor performance and long-term memory and so it did when combined with NBQX. Also retention of the passive avoidance task and motor performance were impaired by valproate alone or given together with NBQX. Finally, NBQX (10 mg/kg) did not affect the plasma level of any antiepileptic drug. It is concluded that non-NMDA glutamate receptor blockade results in the considerable enhancement of the efficacy of common antiepileptic drugs.

Animals↗
PubMed1992

Age dependency of the susceptibility of rats to aminooxyacetic acid seizures.

Immature rats are more susceptible to clonic seizures induced by aminooxyacetic acid (AOAA) than mature and senile rats. Highest susceptibility to AOAA seizures was observed in 7-14-day-old rat pups. The lowest susceptibility was recorded in 10-20 month-old rats. AOAA seizures in 14-day-old rats were blocked by clonazepam and valproate, but not by phenobarbital, carbamazepine, diphenylhydantoin, trimethadione or ethosuximide. Morphological analysis of brains from 14-day- and 3-month-old rats which experienced AOAA seizures did not reveal epilepsy-related damage. These observations suggest that immature rat brain is highly prone to convulsions induced by AOAA and that such convulsions are difficult to control by available antiepileptic treatment.

Aging↗
PubMed1992

Anticonvulsant activity of carbamazepine and diphenylhydantoin against maximal electroshock in mice chronically treated with aminophylline.

The anticonvulsant activities of both carbamazepine and diphenylhydantoin alone (after a single intraperitoneal administration) or combined with aminophylline were studied against maximal electroshock-induced convulsions in male mice. Aminophylline (injected acutely at 50 mg/kg) significantly increased the ED50 values of both antiepileptics. Given for three days, aminophylline (50 mg/kg, twice daily) still impaired the potency of both antiepileptics and after chronic aminophylline administration a further decrease in the protective activity of carbamazepine and diphenylhydantoin was found. Specifically, after 14 days of aminophylline treatment, ED50s for carbamazepine and diphenylhydantoin were 26 and 19 mg/kg, respectively. These ED50s were significantly elevated compared to values determined after acute aminophylline treatment (21.2 and 14.9 mg/kg, respectively). Plasma levels of both antiepileptics were unaffected by chronic aminophylline which seems to exclude a pharmacokinetic interaction in terms of total plasma levels at least. The present results clearly indicate that the aminophylline-induced impairment of the anticonvulsant activity of carbamazepine and diphenylhydantoin is enhanced over time. This may render aminophylline a hazardous drug to epileptic patients who are prescribed this smooth muscle relaxant.

Aminophylline↗
PubMed1992

Influence of flunarizine, nicardipine and nimodipine on the anticonvulsant activity of different antiepileptic drugs in mice.

Only flunarizine (40 mg/kg, i.p.) significantly raised the threshold for electroconvulsions in mice (ear-clip electrodes, 0.2 sec stimulus duration, tonic hindlimb extension as an endpoint), whilst nicardipine and nimodipine (up to 80 mg/kg) was ineffective in this respect. Further, flunarizine (10 and 20 mg/kg) potentiated the efficacy of carbamazepine and valproate against maximum electroshock (50 mA)-induced seizures and, in the dose of 20 mg/kg, enhanced that of diphenylhydantoin. In addition, this calcium channel inhibitor was without influence upon the total levels of these antiepileptics in plasma. Nicardipine (5 and 10 mg/kg) and nimodipine (10 and 20 mg/kg) increased the protective potential of carbamazepine and nimodipine (20 mg/kg) also decreased the ED50 of diphenylhydantoin against maximum electroshock. However, nicardipine distinctly increased the level of carbamazepine in plasma, whilst nimodipine did not affect the level of both antiepileptics in plasma. The combined treatment of calcium channel inhibitors and antiepileptic drugs, providing a 50% protection against maximum electroshock, did not significantly change the motor performance of mice in the chimney test, when compared with antiepileptic drugs, given alone at their ED50s, against maximum electroshock-induced convulsions. The present results give further support to the idea of the combined use of some calcium channel inhibitors and antiepileptic drugs in the treatment of human epilepsy.

Animals↗
PubMed1992

Antiparkinsonian drugs memantine and trihexyphenidyl potentiate the anticonvulsant activity of valproate against maximal electroshock-induced seizures.

Memantine increased the threshold for electroconvulsions, when administered at 1.0-6.0 mg/kg (i.p.) and given in subthreshold doses of 0.0156, 0.0625, 0.125 and 0.5 mg/kg (i.p.) potentiated the protective efficacy of valproate, against maximal electroshock (50 mA)-induced seizures in mice, lowering the ED50 from 235 to 197, 172, 164 and 130 mg/kg, respectively. Trihexyphenidyl, applied in doses of 30 and 50 mg/kg (i.p.), did not influence the electroconvulsive threshold per se but when combined with valproate, strongly enhanced its anticonvulsant activity against maximal electroshock-induced seizures lowering the ED50 from 206 to 103 and 46 mg/kg, respectively. The chimney test and retention testing in mice revealed that administration of memantine at 0.5 mg/kg (i.p.) or trihexyphenidyl at 30 mg/kg (i.p.) together with valproate in doses of 130 or 103 mg/kg (i.p.), respectively, resulted in motor impairment and caused impairment of long-term memory, similar to the effects of valproate alone, when applied at its ED50 against maximal electroshock. Neither memantine nor trihexyphenidyl altered the total level of valproate in plasma. It may be concluded that the potentiation of the anticonvulsant activity of valproate, by memantine and trihexyphenidyl, is not associated with a pharmacokinetic interaction.

Animals↗
PubMed1992

Susceptibility to seizures produced by chemical convulsants and maximal electric shock in rats after electrolytic lesions into the red nucleus.

Bilateral electrolytic lesions into the red nucleus (RN) of rat elicit an increase in susceptibility to seizures induced by pilocarpine, kainic acid, isoniazid, pentylenetetrazole, bicuculline and maximal electric shock (MES). It was also observed that carbachol-induced wet-dog shakes were increased in the RN-lesioned rats. The brain acetylcholine (ACh) and gamma-aminobutyric acid (GABA) concentrations were significantly decreased in the striatum and substantia nigra, respectively. There were no changes in electroencephalogram (EEG) recordings in the RN-lesioned group compared with sham-operated rats. Based on the results it is proposed that the RN is involved in the generalization and acceleration of seizure activity through the cholinergic and GABA-ergic system.

Acetylcholine↗
PubMed1992

Some pharmacological properties of prolonged administration of Ukrain in rodents.

Some pharmacological properties of Ukrain administered intraperitoneally (i.p.) once daily for three months in mice and rats of both sexes were studied. A three month treatment with Ukrain significantly depressed the spontaneous locomotor activity and did not affect the motor coordination of mice and rats of both sexes. Ukrain did not affect the body weight gain as well as the mass of internal organs; the exception was an increase in the mass of the spleen in rats. Biochemical studies indicated that a three month treatment with Ukrain depressed the whole brain dopamine (DA) concentrations and did not affect the noradrenaline (NA) concentrations. Long-term administration of Ukrain showed no characteristic changes in the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the whole brain. The observed changes after three months' treatment with Ukrain are similar in mice and rats of both sexes.

Alkaloids↗