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T Stoytchev

Publications and source records attributed to T Stoytchev.

At least 37 records · Page 2Linked to original sources
PubMed1984

Effect of hydrocortisone and desoxycorticosterone on some reductases, esterases and synthetases.

Corticosteroids, applied in single high doses, are known to inhibit the activity of mixed function oxidases. Experiments on male rats have been performed in order to clarify their effect on other drug-metabolizing enzyme systems. It is found that hydrocortisone (HC) and desoxycorticosterone (DOCA), applied in a single dose of 50 mg/kg, do not change the activity of the liver microsomal NADPH-dependent neotetrazolium reductase. HC inhibits the intestinal acetylsalicylic esterase B, whereas DOCA does not change it significantly. This effect should be borne in mind when combining corticosteroids with acetysal. No significant changes are observed in the activity of liver esterase A under the effect of the two corticosteroids. DOCA inhibits the liver cytosol glutathione-S-transferase. The reduced enzyme activity of the liver microsomal UDP-glucuronyl-transferase by the two corticosteroids and of the glutathione-S-transferase by HC is manifested only as an insignificant tendency.

Animals↗
PubMed1984

Toxicological studies on the acute and subchronic toxicity of two new derivatives of 3,3-diethyl-2,4-pyridinedione.

The acute and subchronic toxicity (30 days) of N-aminomethylmorpholine-3,3-diethyl-2,4-pyridinedione (DKMM) and N-aminomethyl-piperazine-3,3-diethyl-2,4-pyridinedione (DKMP) was studied. The two compounds were found to have low acute toxicity. No changes are found in the haematological, urological and biochemical parameters, as well as in the histological tests of liver and parts of the cerebrum, after subchronic treatment with doses 150 there is an increase in GOT, GPT and the acid phosphatase. These results also correlate with the histological studies of the liver. The results of the acute toxicity show that DKMM and DKMP are weakly toxic substances (LD50 above 1500 mg/kg). Under conditions of the subchronic experiment the substances were tolerated very well by the animals, without causing lethality and essential toxicological changes in the organs studied.

Animals↗
PubMed1984

Changes in rat liver and brain monoamine oxidase activity after acute treatment with some heavy metal salts.

In in vivo and in vitro experiments the effects of some heavy metal salts (Cu, Co, Cd, Pb, Ni, Zn, Hg, As, Bi and Sn) on rat liver and brain mitochondrial monoamine oxidase (MAO) activity was studied using three different substrates (tyramine, 5-hydroxytryptamine (5-HT) and beta-phenylethylamine (2-PEA). It was established that some of the metals (Cu, Cd, Bi) inhibited MAO activity both in vivo and in vitro experiments, others like Ni, Zn, As and Sn inhibited it only in vivo while Hg exerted inhibitory action only in vitro. The in vivo experiments showed significantly higher sensitivity of brain MAO as compared with liver MAO to the inhibitory action of metals. The same higher susceptibility was shown by liver and brain MAO-A form. It was concluded that the inhibitory effects of some heavy metal salts on MAO activity were not directly connected with their action on enzyme thiol groups but more probably with changes in the enzyme membrane surroundings in the different organs.

Animals↗
PubMed1984

Generalized epilepsy induced by kainic acid and anticonvulsant effect of N-aminomethylpiperazine-3,3-diethyl-2,4-pyridinedione.

Systemic administration of kainic acid in rats (30 mg/kg s.c.) and cats (5 mg/kg i.p.) produced after a definite period (30 to 60 min) secondary generalized seizures occurring first in the limbic structures (amygdala and hippocampus). The effect of N-aminomethylpiperazine-3,3-diethyl-2,4-pyridinedione (DKMP) at a dose of 100 mg/kg i.v. was evaluated on the background of developed kainic epilepsy. In rats, DKMP inhibited kainic clonic and tonic seizures and 100% of the animals survived. The drug was ineffective against limbic seizures. In cats, DKMP strongly suppressed the cortical EEG paroxysmal activity and slightly influenced the limbic one. The present data contribute to the knowledge of the anticonvulsive activity of DKMP, showing it to be a promising antiepileptic drug with mainly cortical action.

Animals↗
PubMed1984

Comparative study of the anticonvulsive activity of N-aminomethylpiperazine-3,3-diethyl 2,4-pyridinedione with the activity of known antiepileptic agents.

N-aminomethylpiperazine-3,3-diethyl-2,4-pyridinedione (DKMP) is a newly synthesized compound with a marked anticonvulsive effect in various epileptic models. The aim of the present work is to compare its anticonvulsive effect in corazol convulsions (100 mg/kg corazol, s.c.) with known anticonvulsants applied in clinical practice. The compounds tested were applied subcutaneously in equitoxic doses (1/20 and 1/30 of their respective LD50). Some undesirable side effects of the antiepileptic agents tested were also studied. With the experimental model used, DKMP was found to have a better anticonvulsive effect compared with diphenylhydantoin, depakin, suxilep and phenobarbital. Diazepam completely inhibited the convulsions, but it has an undesirable strong myorelaxing effect. In a subchronical experiment it was found that no tolerance developed toward DKMP, while the anticonvulsant effect of diazepam significantly decreased on the 15th day, compared with a single administration. Using the rota-rod test it was found that the agents studied had a stronger neurotoxic action compared with DKMP. These results outline DKMP as a promising compound with good antiepileptic activity, comparable to that of the known anticonvulsants.

Animals↗
PubMed1984

Hepatic mixed-function oxidase system and microsomal lipid peroxidation in rats treated with a synthetic immunomodulator, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP).

Effects of synthetic muramyl dipeptide (MDP) on activity of liver microsomal mixed-function oxidase system and on the susceptibility of liver microsomes to lipid peroxidation, were tested in rats at intervals of 1 or 24 hours after single i.p. injection of MDP (1 mg per animal). No significant changes were found in levels of cytochrome P-450 and b5, microsomal heme, or in activities of aniline hydroxylase, ethylmorphine demethylase, glucuronide transferase or cytosol glutathione-S-transferase. However, significantly less (about 45%) TBA-reactive material accumulated in microsomal samples at the 1 h-interval after the MDP administration. The same inhibitory effect of MDP on lipid peroxidation was shown in vitro (in 1 mM concentration) after incubation of microsomes with the NADPH/ADP/Fe system.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Heavy metals and enzyme induction.

In experiments on male albino rats it was established that single toxic doses of heavy metal salts inhibited to a different extent the enzyme-inducing action of phenobarbital and methylcholanthrene as determined by ethylmorphine-N-demethylase, respectively aniline hydroxylase activity. The majority of salts (of Cu, Co, Cd, Pb, Ni, Zn and Hg) inhibited more strongly the enzyme induction produced by methylcholanthrene as compared with that caused by phenobarbital. Subtoxic doses of Co, Cd, Zn and Ni salts given daily with the drinking water for 30 days shortened the hexobarbital sleeping time and increased the ethylmorphine-N-demethylase activity and cytochrome P-450 content in the liver microsomes. This suggests an enzyme-inducing action of these heavy metal salts at oral administration in subtoxic doses. Cu, Bi, Sn, Pb did not produce enzyme induction. The changes in the three indices of the As and Hg action were not consistent in our experiments.

Animals↗
PubMed1983

Enzyme-inhibiting action of hydrocortisone and desoxycorticosterone of mixed function oxidases.

Comparative studies have been carried out on the action of two corticosteroids: the mineralocorticoid desoxycorticosterone and the glucocorticoid hydrocortisone, upon single administration in male albino rats, on the hexobarbital sleeping time and the activity of the mixed function oxidases. Applied in equimolar doses, the two steroids prolong the hexobarbital sleeping time, the effect of desoxycorticosterone being stronger. The potentiation of hexobarbital sleeping time by hydrocortisone differs in degree in animals from the different age groups, being most pronounced in mature animals compared with two-week-old immature and old animals. Unlike hydrocortisone, the potentiating effect Of desoxycorticosterone is close in intensity for all age groups studied. Both corticosteroids in single doses (50 mg/kg) inhibit the activity of mixed function oxidases, metabolizing type I substrates--hexobarbital and morphine, the inhibitory effect of desoxycorticosterone being stronger. Hydrocortisone does not influence the metabolism of type II substrates (aniline), while desoxycorticosterone inhibits it considerably. The reasons for the differences observed in the effects of the two compounds are sought in the different involvement of the enzyme systems studied in their metabolism.

Age Factors↗
PubMed1983

Effect of cadmium in vitro on benzphetamine-N-demethylation and ethoxyresorufin-O-deethylation in rats of different age.

The in vitro influence of CdSO4 on the liver microsomal benzphetamine-N-demethylation and ethoxyresorufin-O-deethylation activities in male Wistar rats/age 10, 30, 60 and 240 days/as well as the type of inhibition were studied after phenobarbital or beta-naphthoflavone pretreatment. Both reactions were inhibited by CdSO4 in dependence on concentration in all age groups. After phenobarbital pretreatment the inhibition of N-demethylation was slightly pronounced in 10-day old rats. In 10 and 30-days old rats the type of inhibition was competitive while in 60 and 240-days old rats a non-competitive type of inhibition was observed. O-deethylation of ethoxyresorufin was inhibited also in 10-day old rats, the inhibition type was non-competitive in all age groups. After beta-naphthoflavone pretreatment N-demethylation was inhibited competitively in all age groups. The inhibition of O-deethylation was more pronounced in 30-day old rats, in other age groups the inhibition was weak but concentration dependent. The type of inhibition was noncompetitive for all age groups studied.

Aging↗
PubMed1983

Neuropharmacological activity of newly-synthesized derivatives of 3,3-diethyl-2,4-pyridinedione. V. Relation between chemical structure and pharmacological activity.

On the basis of neuropharmacological screening of newly-synthesized derivatives of 3,3-diethyl-2,4-pyridinedione ( Pyrithyldion ) some regularities are pointed out, related to the link between the chemical structure and the pharmacological activity of the pyridinedione derivatives. The following groups of compounds were studied: N-acyl, N-alkyl, N-amino-methyl, 5- acyloxymethyl and 5-aminomethyl. The derivatives tested were found to be biologically active substances with central depressant action differing from that of pyridinedione. Most generally, it may be stated that substitution of the pyridinedione nucleus with N-alkyl and 5-aminomethyl radicals results in compounds with analgesic action without soporific effect, while substitution with N-aminomethyl radicals leads to compounds with marked anticonvulsive activity and manifestation of soporific effect in high doses (1/2 of the lethal doses).

Amphetamine↗
PubMed1983

Central depressive action of two N-aminomethyl derivatives of diethylpyridinedione.

The central depressive action of N-aminomethylmorpholine-3,3-diethyl-2,4-pyridinedione (DKMM) and N-aminomethylpiperazine-3,3-diethyl-2,4-pyridinedione (DKMP), compounds having a marked anticonvulsive effect, has been studied applying a set of methods characterizing this action. DKMM and DKMP are found to prolong hexobarbital, chlorhydrate and alcohol sleeping time. Investigated by the modified jumping test, the two substances inhibit the central nervous system to the same degree. They show at the same time properties of hypnosedatives and neuroleptics as well. DKMM and DKMP manifest motor-incoordination activity in doses nearly 3.5 times higher than the doses inhibiting corazol convulsions. The compounds have a marked antiaggressive effect in the case of isolation syndrome, particularly pronounced for DKMP in a dose of 1/12 of LD50. The results obtained show that DKMM and DKMP are central depressants with marked sedative-tranquillizing action.

Aggression↗
PubMed1980

Effect of hydrocortisone on oxidative degradation of hexobarbital and ethylmorphine.

In experiments on albino rats of both sexes it has been established that hydrocortisone applied in a single dose of 50 mg/kg i.p. inhibits hexobarbital oxidase and ethylmorphine-N-demethylase and applied repeatedly in a dose of 10 mg/kg increases the activity of both enzymes. In castrated male rats the enzyme-inhibiting action of the single dose of hydrocortisone is much reduced, while its enzyme-inducing action on repeated application remains the same (the two effects are evaluated by the hexobarbital sleeping time).

Animals↗
PubMed1980

Effect of acute intoxication with some heavy metals on drug metabolism.

In experiments on male albino rats after subcutaneous injection of a single toxic dose it was found that copper sulphate (CuSO4), cobaltous nitrate (Co(NO3)2, cadmium sulphate (CdSO4), lead acetate Pb(CH3COO)2 significantly inhibited the hexobarbital-oxidazing enzyme system, while with Nickel sulphate (NiSO4), Zinc sulphate (ZnSO4), Arsenic trioxide (As2O3), Mercuric chloride (HgCl2), Bismuth [Bi(NO3)2] and stannous chloride (SnCl2) the differences were insignificant. Aniline hydroxilase was significantly inhibited by CuSO4, Co(NO3)2, CdSO4, Pb(CH3COO)2, NiSO4, and As2O3 and not inhibited at all by HgCl2. Bi(NO3)2, SnCl2, and ZnSO4. In determination of ethylmorphine demethylase activity CuSO4, Co(NO3)2, CdSO4, and NiSO4 significantly inhibited the enzyme activity, while with the other salts the differences were insignificant. The metals which exerted an inhibitory effect on the above-mentioned enzymes reduced also the microsomal cytochrome P-450 content.

Animals↗
PubMed1980

Effect of papaverine analogues on 3', 5'-adenosine monophosphate phosphodiesterase activity in rat brain.

In vitro studies were carried out of some hydrated papaverine analogues on the rat cerebral phosphodiesterase (PD). The potential inhibitory effect of the newly-synthesized drugs (Trifonov, Orahovats, 1978), as well as the effect of papaverine, were studied in a series of concentrations (1 micrometer to 100 micrometers) on brain homogenates. The enzyme activity was determined by the isotope method of Filburn and Karn (1972) at two substrate concentrations (1 and 200 micrometers). Dihydropapaverine was found to have practically no effect. 6'-Iodo-dihydropapaverine is a weaker inhibitor of the enzyme with low Km, compared with 6'-bromo-dihydropapaverine, however, unlike it its effect on PD with high Km is more marked. Among the compounds tested, papaverine is the most powerful inhibitor of the enzyme with low and high Km. The kinetic analysis of PD with low and with high Km, performed after Lineweaver and Burk, has shown hat the inhibition of the enzyme by the studied substance is reversable and of the competitive type. The inhibitory constants of the compounds studied were estimated.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Influence of the acute intoxication with salts of some heavy metals on hexobarbital sleep and hexobarbital metabolism.

The effect of acute intoxication with salts of ten heavy metals on hexobarbital sleep and the dependence of this effect on the time of application and the dose of the heavy metal are studied in experiments on male albino rats. Two hours after subcutaneous injection of toxic doses, only cobalt nitrate significantly prolongs hexobarbital sleep. Significant prolongation of the sleep is observed at the 24th hour in intoxication with CuSO4, CdSO4, Co(NO3)2, Pb(CH3COO)2, ZnSO4, NiSO4, while As2O3, HgCl2, Bi(NO3)2 and SnCl2 do not change it. All heavy metals (with the exception of NiSO4) prolong significantly hexobarbital sleep 96 hours after the intoxication. At the 24th hour after intoxication with salts of heavy metals, the hexobarbital level in the blood serum at the 30th min after its administration is significantly higher for Co(NO3)2, CdSO4, NiSO4, and it tends to be higher for CuSO4 and Pb(CH3COO)2. This, together with the significant inhibition of the hexobarbital-oxidizing enzyme system in the case of Cu, Co, Cd and Pb, suggests that in the case of these heavy metals potentiation of the hexobarbital sleep is largely due to inhibition of the hexobarbital metabolism. No significant prolongation of hexobarbital sleep or changes in hexobarbital metabolism are found in intoxication with Hg, As, Bi and Sn salts. The definitely lower hexobarbital level in the blood serum and brain at the waking moment, as well as the lower threshold hypnotic doses, suggest the interference of pharmacodynamic mechanisms at the level of the central nervous system in the prolongation of hexobarbital sleep after acute intoxication with CuSO4, CdSO4 and NiSO4.

Acute Disease↗
PubMed1979

Neuropharmacological activity of new derivatives of 3,3-diethyl-2,4-pyridinedione. IV. 1-alkyl derivatives of 3,3-diethyl-2,4-pyridinedione.

Neuropharmacological screening of five 1-alkyl derivatives of 3,3-diethyl-2,4-pyridinedione was performed on male albino mice. The substances studied manifest very good analgesic effect in the test involving intraperitoneal injection of glacial acetic acid. 1-Alkyl derivatives have no hypnotic effect. They potentiate hexobarbital anaesthesia (with the exception of 1-/4'-/2''-hydroxyethyl/-piperazinylpropano/-3,3-diethyl-2,4-pyridinedione). 1-/2-morpholinoethyl/-3,3-diethyl-5-hydroxymethyl-2,4-pyridinedione and 1-/2'-morpholinoethyl/-3,3-diethyl-5-/3',4',5'-trimethoxybenzoyloxymethyl/-2,4-pyridinedione inhibit the amphetamine-stimulated motor activity. The newly-synthesized substances have no anticonvulsant action in corazol convulsions. 1-Alkyl derivatives are found to manifest a central depressive action, differing from that of diethylpyridinedione.

Analgesics↗
PubMed1978

Effect of subacute intoxication with some heavy metals on hexobarbital sleep and metabolism.

In experiments on albino rats it is found that cobaltous dichloride, cadmium nitrate, nickel sulphate, copper sulphate and lead acetate, applied subcutaneously for 7 days, potentiate hexobarbital anaesthesia, while mercury dichloride and iron dichloride have no effect on it. A higher hexobarbital content is found in the blood serum of rats, treated with cobaltous dichloride, cadmium nitrate, nickel sulphate, copper sulphate and lead acetate, compared with the control animals. Treatment for 7 days with cobalt dichloride, cadmium nitrate, copper sulphate and nickel sulphate inhibits the activity of the liver microsomal hexobarbital-oxidizing enzyme system. The prolonged hexobarbital sleep in rats subjected to subacute intoxication with cobalt, cadmium, nickel, copper and lead is probably due to a considerable extent to the inhibition of the hexobarbital metabolism by these metals.

Animals↗