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Biomedical subjects

Z Kleinrok

Publications and source records attributed to Z Kleinrok.

At least 307 records · Page 17Linked to original sources
PubMedDate not supplied

Influence of different methylxanthines on the anticonvulsant action of common antiepileptic drugs in mice.

The protective activity of carbamazepine (CBZ, 60 min before testing), phenobarbital (PB, 120 min), phenytoin (PHT, 120 min), and valproate (VPA, 30 min) alone or concurrent with methylxanthine derivatives was evaluated against maximal electroshock-induced seizures (MES) in male mice. All drugs were administered intraperitoneally (i.p.), and the protection offered by antiepileptic drugs (AEDs) was expressed as ED50 in mg/kg. Caffeine sodium benzoate in doses of 0.0595-0.476 mmol/kg (11.55-92.4 mg/kg) distinctly reduced the anticonvulsant efficacy of PB, in the highest dose tested with an increase in ED50 value from 19.5 to 38 mg/kg. This methylxanthine derivative in the dose range of 0.119-0.476 mmol/kg (23.1-92.4 mg/kg) also efficiently inhibited the protective action of PHT. When combined with caffeine (0.238 and 0.476 mmol/kg), the ED50 of PHT was raised from 12 to 17 and 24 mg/kg, respectively. In doses of 0.238 and 0.476 mmol/kg, caffeine also diminished the efficacy of CBZ and VPA, and at the highest dose tested the methylxanthine elevated the respective ED50s from 13 to 20.5 mg/kg and from 270 to 420 mg/kg. Generally caffeine sodium benzoate (up to 0.476 mmol/kg) did not affect the plasma levels of studied AEDs, and only at 0.476 mmol/kg did it significantly decrease the level of PHT. Among the other methylxanthines, pentoxifylline (0.238-0.476 mmol/kg; 66.3-132.5 mg/kg) and diprophylline (0.952 mmol/kg; 242.1 mg/kg) inhibited the protective potential of PHT and the respective ED50s were raised from 12 to 16.5, 15.5, and 14 mg/kg. No significant alterations in PHT plasma levels were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMedDate not supplied

Influence of chronic aminophylline on the anticonvulsant efficacy of phenobarbital and valproate in mice.

The protective efficacy of phenobarbital (PB, 120 min before testing) and valproate (VPA, 30 min before testing) alone or combined with aminophylline (a single dose of 50 mg/kg, 3-day or 14-day administration twice daily 50 mg/kg at 8.00 a.m. and 8.00 p.m.) was evaluated against maximal electroshock-induced seizures (MES) in male mice. All drugs were given intraperitoneally (i.p.), and the protection provided by PB and VPA was evaluated as the respective ED50 value (in mg/kg). Aminophylline in a single dose of 50 mg/kg (30 min before electroconvulsions) distinctly reduced the protective efficacy of both PB and VPA, reflected by the increase in the respective ED50 values from 22 to 31 mg/kg (p < 0.001) for PB and from 247 to 281 mg/kg (p < 0.001) for VPA. After administration of aminophylline for 3 days (electroshock was performed 30 min after the last aminophylline injection), the respective ED50 values for PB and VPA were 29.5 (p < 0.01) and 269 mg/kg (p < 0.01 vs. saline-treated animals). Chronic treatment with aminophylline (14 days) resulted in further impairment of the protective activity of PB and VPA. Specifically, the ED50 value of PB was 39 mg/kg (p < 0.05 vs. PB+single injection of aminophylline) and that of VPA was 318 mg/kg (p < 0.01 vs VPA+single injection of aminophylline). Plasma levels of both PB and VPA were not affected by chronic aminophylline; moreover, the plasma level of theophylline was even lower after chronic aminophylline as compared with single aminophylline administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗
PubMedDate not supplied

Evidence for intraocular synthesis of kynurenic acid, a putative endogenous neuroprotectant.

Kynurenic acid (KYNA), an excitatory amino acid antagonist preferentially active at glycine binding site of the NMDA receptor, has been previously identified in the brain. This study was designed to examine its presence in the rabbit vitreous humor. Mean (+/- SD) level of KYNA in the vitreous was 22.3 +/- 3.9 pmol/ml as determined by HPLC. Intravitreal administration of 10 mmol aminooxyacetic acid (AOAA), a KYNA synthesis inhibitor, diminished its production by 9.6% after 2 h, 47.8% after 24 h and 21.5% after 48 h. It can be concluded that AOAA decreases the intravitreal concentration of KYNA, providing evidence of its intraocular origin.

Aminooxyacetic Acid↗
PubMedDate not supplied

Behavioral studies of the effects of moderate oligemic hypoxia caused by bilateral clamping of carotid arteries in mice. Impairment of spatial working memory.

The experiments carried out on Albino Swiss mice indicated that bilateral clamping of carotid arteries (BCCA) for 30 min caused no neuronal damage but produced an increase in GABA content in the hippocampus, striatum and frontal cortex. The behavioral studies have shown that BCCA did not influence the motor coordination, the spontaneous locomotor activity, the reactivity to pain and the cataleptic response to haloperidol of the mice. However, a significant increase in amphetamine-induced hyperactivity was observed after BCCA. In mice, BCCA did not impair long-term memory and spatial working memory, reflected by alternation behavior in the Y-maze. The same dose of scopolamine impaired the working memory in mice which underwent BCCA much more than sham-operated controls. Naftidrofuryl improved the working memory in mice subjected to BCCA as measured 48 h after the surgery. Pretreatment with naftidrofuryl protected the animals against the impairment of alternation behavior caused by scopolamine administration.

Anesthesia↗
PubMedDate not supplied

The effect of bradykinin on central dopamine receptors.

Bradykinin (BK) injected intraventricularly (ivc) at doses of 0.25-0.5 mug per rat potentiated the depth of fluphenazine catalepsy and depressed or abolished the symptoms of sterotypy produced by amphetamine or apomorphine. BK did not affect the level of dopamine (DA), but elevated the level of homovanillic acid in the brain, and accelerated DA turnover as measured by the rate of dopamine disappearance following treatment with alpha-methyltyrosine. The results suggest that BK inhibits the central dopamine structures by blocking the DA receptors.

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PubMedDate not supplied

Pharmacological properties of some xanthone derivatives.

A series of aminoalkanolic derivatives of xanthone were examined in some experimental models of epilepsia, i.e., pilocarpine, aminophylline and pentetrazole-induced seizures. A final objective of this research was to examine the action of these compounds on the central nervous system, namely on spontaneous locomotor activity, amphetamine-induced hyperactivity and narcotic sleep induced by hexobarbital, as well as their influence on the gamma-aminobutyric acid (GABA) level and glutamic acid decarboxylase (GAD) activity in mice brain. The most interesting were the pharmacological results of (R)-2-N-methylamino-1-butanol derivative of 7-chloro-2-methylxanthone [Id], which displayed protective activity against the seizures induced by maximum electroshock and pentetrazole induced seizures; moreover, this compound had a relatively low toxicity and did not exhibit a neurotoxic effect. The influence on the locomotor activity as well as on the amphetamine-induced locomotor hyperactivity in mice was also seen for Id. Compound Id did not decrease the GABA level in mice brain.

Aminophylline↗
PubMedDate not supplied

Antiplatelets activity of some xanthone derivatives.

The effects of twelve aminoalkanolic derivatives of xanthone on platelet aggregation have been evaluated. Five from them inhibited thrombin-induced platelet aggregation. The most active compound was R-(+)-2-N-(7-chloro-2-xanthonemethyl)-2-N-methylamino-1-butanol [IV] which, at a concentration of 40 micrograms/ml, nearly completely inhibited the aggregation concentration (TAC) of thrombin.

Animals↗
PubMedDate not supplied

Two essential amino acids, L-lysine and L-histidine, in five types of experimental seizures.

L-Lysine (250-2,000 mg/kg) and L-histidine (1,000-2,000 mg/kg) significantly raised the electroconvulsive threshold. D-Histidine (1,000 mg/kg) was completely ineffective in this regard. Both amino acids were generally inactive in pentetrazole-, picrotoxin- and aminophylline-induced seizures, though L-histidine (2,500 mg/kg) significantly reduced the number of mice with clonic convulsions in the pentetrazole test. Also, L-lysine (2,500 and 3,000 mg/kg) significantly diminished mortality rate in aminophylline-induced seizures. In addition, L-lysine (2,500-3,000 mg/kg) and L-histidine (2,000-2,500 mg/kg) delayed the onset of aminophylline- and picrotoxin-evoked convulsions. L-Lysine and L-histidine (both up to 1,000 mg/kg) did not affect amygdala-kindled seizures in rats. The results indicate that some of indispensable amino acids may play a role in the inhibitory transmission in the central nervous system. A possibility arises that appropriate diet may be an important supportive factor in the treatment of some epileptic patients, probably suffering from generalized tonic-clonic seizures.

Aminophylline↗
PubMedDate not supplied

Anticonvulsant action of chlormethiazole is prevented by subconvulsive amounts of strychnine and aminophylline but not by bicuculline and picrotoxin.

The anticonvulsant action of chlormethiazole was evaluated with the use of subthreshold doses of convulsants affecting the purinergic, glycinergic and gamma-aminobutyric acid (GABA)-mediated transmission, i.e. aminophylline, strychnine, bicuculline and picrotoxin in the model of generalized tonic-clonic convulsions. Chlormethiazole protected mice against maximal electroshock-induced seizures with an ED50 of 130.8 mg/kg. Aminophylline (100 mg/kg) and strychnine (0.4 mg/kg) reversed the protective action of chlormethiazole against electroconvulsions raising the ED50 values of this drug to 218.6 and 208.6 mg/kg, respectively. In contrast, GABA antagonists, bicuculline and picrotoxin, neither affected the protection provided by chlormethiazole nor did they alter the protective activity of valproate, phenobarbital, diphenylhydantoin and carbamazepine against electroconvulsions. Our results indicate that (a) the anticonvulsant activity of chlormethiazole might be related to its interaction with strychnine-sensitive glycinergic as well as purinergic neurotransmission, (b) purinergic and strychnine-sensitive glycinergic events contribute more prominently than GABAergic ones to the anticonvulsant activity of the drugs providing protection against maximal electroshock-induced convulsions.

Aminophylline↗
PubMedDate not supplied

GABA content and GAD activity in gastric cancer.

BACKGROUND: Several recent reports have suggested a connection between the GABA-ergic system and neoplastic processes. It has been confirmed that both GABA content and GAD activity, are increased in neoplastic tissues in colon and breast cancer. In the light of the theory of dynamic balance between stimulating and inhibitory amino acids, disturbances in GABA metabolism may be an expression of the cell's defensive response to the neoplastic process. The aim of the present study was to evaluate GABA content and GAD activity in the tissue from gastric cancer and in the macroscopically unchanged wall of the stomach. MATERIAL AND METHODS: GABA content and GAD activity were evaluated in tissue material obtained from 34 patients operated for gastric cancer. GABA and GAD levels were determined in neoplastic tissue and surrounding unchanged tissue by spectrofluorometric method. RESULTS: The investigations revealed that the GABA content and GAD activity were significantly higher in the neoplastic tissue in comparison to the unchanged tissue of the stomach. CONCLUSION: The results obtained, together with reports from the literature, suggest the possibility of introducing GABA-ergic system agonists into adjuvant therapy in gastric cancer.

Adult↗
PubMedDate not supplied

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. At a dose of 1.25 mg/kg, both drugs significantly elevated the threshold. D(-)CPP (0.625 mg/kg) and (+/-)CPP (0.625 mg/kg) potentiated the anticonvulsant activity of valproate, carbamazepine and phenobarbital. No potentiation was observed in the case of diphenylhydantoin. Moreover, these competitive NMDA antagonists did not influence the plasma levels of antiepileptic drugs, so a pharmacokinetic interaction, in terms of total and free plasma levels at least, is not probable. The combined treatment of both CPP agents with either carbamazepine, diphenylhydantoin or phenobarbital (providing a 50% protection against maximal electroshock) was devoid of significant side effects (in the tests evaluating motor and long-term memory impairment). Valproate co-administered with CPP compounds caused a moderate motor impairment, but did not affect cognitive functions in mice. It is noteworthy that valproate and phenobarbital given alone at doses equal to their ED50s resulted in significant long-term memory deficit. The results indicate that combinations of antiepileptic drugs with some NMDA receptor antagonists, apart from enhanced anticonvulsant potential, may not necessarily result in the occurrence of considerable adverse reactions.

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PubMedDate not supplied

The central action of intraventricularly (ivc) administered propranolol and phentolamine in rat.

Propranolol (100mug) ivc together with phentolamine (60 mug) decreased spontaneous locomotor activity and weakened post-nialamide locomotor activity in rat. When applied separately in the above doses, neither of the two compounds had this action. Depression of amphetamine-induced locomotor activity was observed after propranolol (250 mug) together with phetolamine (60 mug). Phentolamine alone, had hypothermic action but when applied together with propranolol, it increased after 4 hrs body temperature. The tested compounds prolonged hexobarbital-induced sleeping time but did not affect noradrenaline or dopamine levels in rat's brain.

Animals↗