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1.
Biomed Khim ; 66(2): 130-137, 2020 Feb.
Artigo em Russo | MEDLINE | ID: mdl-32420893

RESUMO

Protein kinase CK2 is an important enzyme in the nervous system. The nuclear forms of CK2 regulate chromatin structure and gene expression, the key processes for long-term memory formation. Memory modulators, the Structural Analogues of Etimizole (SAE), were able to increase or decrease the activity of chromatin-associated CK in the cortex and hippocampus of rat brain in vitro. In vivo memory enhancers from SAE-group (3 mg/kg) stimulated CK2 activity and the transcriptional ability of chromatin in the cortex and hippocampus, starting from 30 min with a peak for 60 min and a duration up to 180 min. At these periods the memory inhibitor from the SAE-group reduced CK2 activity and chromatin transcription. It is assumed that the modulating effect of SAE on CK2 activity and transcription underlies the effects of these compounds on long-term memory.


Assuntos
Caseína Quinase II/metabolismo , Córtex Cerebral/efeitos dos fármacos , Cromatina , Etimizol/análogos & derivados , Etimizol/farmacologia , Hipocampo/efeitos dos fármacos , Animais , Fosforilação , Ratos , Transcrição Genética
2.
Eksp Klin Farmakol ; 70(3): 62-8, 2007.
Artigo em Russo | MEDLINE | ID: mdl-17650638

RESUMO

Ethymisole, or 4,5-di(N-methylcarbamoyl)-1-ethyl-imidazole, is a cognitive enhancer and nootropic drug, the molecular target of which is a multifunctional protein kinase C K2 (casein kinase II). New data about signal pathways and protein substrates of CK2 have been obtained due to research effort of many laboratories. The paper presents a historical sketch of molecular investigations underlying memory enhancer effects of ethymisole; this and the other pharmacological effects of ethymisole are considered in the light of new data.


Assuntos
Caseína Quinase II/metabolismo , Etimizol/farmacologia , Fármacos Neuroprotetores/farmacologia , Nootrópicos/farmacologia , Animais , Caseína Quinase II/genética , Etimizol/química , Humanos , Fármacos Neuroprotetores/química , Nootrópicos/química , Ratos
3.
Patol Fiziol Eksp Ter ; (2): 26-8, 2004.
Artigo em Russo | MEDLINE | ID: mdl-15208927

RESUMO

The aim of the study was assessment of ethimizol effects on fatigue of respiratory muscles and ventilatory disorders caused by inspiratory resistive load on respiration. Cat experiments showed that administration of ethimizol in inspiratory fatigue reestablishes total bioelectric activity of the inspiratory muscles and diaphragmatic nerve, diminishes useful respiratory cycle and respiration rate. Thus, ethimizol in a 1 mg/kg dose i.v. compensates inspiratory muscular fatigue via central mechanism of action.


Assuntos
Etimizol/farmacologia , Fadiga Muscular/efeitos dos fármacos , Músculos Respiratórios/efeitos dos fármacos , Animais , Gatos , Respiração/efeitos dos fármacos
4.
Neurosci Behav Physiol ; 33(8): 799-804, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14635996

RESUMO

The experiments described here demonstrate that disruption of the phosphorylation of transcription factors of the HMG cAMP/Ca-independent protein kinase CK2 class may be the cause of decreased gene expression in age-related cognitive deficits. Amnesia for a conditioned passive avoidance reaction (CPAR) in aged rats (24 months old) was accompanied by decreases in the synthesis of synaptosomal proteins and transcription in nuclei isolated from cortical, hippocampal, and striatal neurons. There was a decrease in chromatin protein kinase CK2 activity and a significant decrease in the phosphorylation of HMG14 by protein kinase CK2. Selective activators of protein kinase CK2 (1-ethyl-4-carbamoyl-5-methylcarbamoylimidazole and 1-ethyl-4,5-dicarbamoylimidazole) increased HMG14 phosphorylation by protein kinase CK2, increased transcription, increased the synthesis of synaptosomal proteins, and decreased amnesia for the CPAR in aged rats. Thus, activation of the "protein kinase CK2-HMG14" system is accompanied by optimization of synaptic plasticity in aged animals. The results provide evidence for the high therapeutic potential of protein kinase CK2 activators.


Assuntos
Envelhecimento/fisiologia , Amnésia/metabolismo , Caseína Quinases , Proteínas de Ligação a DNA/metabolismo , Etimizol/análogos & derivados , Proteína HMGN1/metabolismo , Proteínas Quinases/metabolismo , Amnésia/enzimologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Núcleo Celular/metabolismo , Modelos Animais de Doenças , Etimizol/farmacologia , Leucina/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Ratos , Retenção Psicológica/efeitos dos fármacos , Sinaptossomos/metabolismo , Transcrição Genética/efeitos dos fármacos , Trítio/metabolismo , Uridina Monofosfato/metabolismo
5.
Ross Fiziol Zh Im I M Sechenova ; 88(5): 612-8, 2002 May.
Artigo em Russo | MEDLINE | ID: mdl-12136729

RESUMO

It has been shown that a decrease in HMGs transcription factors phosphorylation by protein kinase CK2 may be the cause of a gene expression decline in cognitive disorders. Passive avoidance amnesia in old rats (24 month) was accompanied by a decrease in synaptosomal protein synthesis and transcription in isolated nuclei of cortex, hippocampus, and striatum. A decrease in chromatin protein kinase CK2 activity and a significant decrease in HMG14 phosphorylation by CK2 was found in old rats. CK2 selective activators, a 4-carbamoyl-5-N-methylcarbamoyl-1-ethyl-imidazole and 4,5-dicaramoyl-1-ethyl-imidazole, produced the HMG14 phosphorylation and transcription activation in old rats. At the same time, synaptosomal protein synthesis activation and passive avoidance amnesia reduction were observed in old rats. Thus, activation of CK2-HMG14 was accompanied by synaptic plasticity optimisation. The data show a high therapeutic potential of activators of CK2-HMG14.


Assuntos
Envelhecimento/metabolismo , Etimizol/análogos & derivados , Proteína HMGN1/metabolismo , Memória , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/anatomia & histologia , Encéfalo/citologia , Encéfalo/metabolismo , Caseína Quinase II , Cromatina/metabolismo , Condicionamento Operante/efeitos dos fármacos , Ativadores de Enzimas/farmacologia , Etimizol/farmacologia , Proteína HMGN1/genética , Masculino , Memória/efeitos dos fármacos , Neurônios/metabolismo , Fosforilação , Ratos , Tempo de Reação , Transcrição Genética/efeitos dos fármacos
6.
Lik Sprava ; (2): 64-8, 2002.
Artigo em Ucraniano | MEDLINE | ID: mdl-12073265

RESUMO

Different therapeutic regimens were tried in 67 patients with hepatic cirrhosis and in 54 patients with chronic hepatitis depending on the leading pathological syndrome. Treatment schemes involved the use of the drug ornicetil in patients having acute episodes of portal systemic encephalopacy, lactulose in those presenting with an increased content of ammonia in the blood and symptoms of chronic portal systemic encephalopacy; etimizol was given to those patients with an apperant antioxidant imbalance. Differentiated approaches to the institution of curative measures permitted improving considerably the patients' medical rehabilitation, achieving regression of pathological manifestations. It has been found out that the above drugs exert a positive effect on the cytolytic and mesenchimal-inflammatory syndromes and will, we believe, come to be widely used for treating diffuse lesions of the liver.


Assuntos
Etimizol/uso terapêutico , Lactulose/uso terapêutico , Hepatopatias/tratamento farmacológico , Nifedipino/uso terapêutico , Ornitina/análogos & derivados , Ornitina/uso terapêutico , Encefalopatia Hepática/tratamento farmacológico , Hepatite Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Pessoa de Meia-Idade , Resultado do Tratamento
7.
Ontogenez ; 30(4): 302-6, 1999.
Artigo em Russo | MEDLINE | ID: mdl-10519132

RESUMO

We studied the effect of propyl- and ethylnorantifein on chloridine-induced abnormalities of extremities in rat embryos. Chloridine (50 and 25 mg/kg, given through the gastric tube) was administered to rats on day 14 of pregnancy, and its embryotoxic effect was estimated from the state of fetuses and implantation sites on day 20 of prenatal development. Propylnorantifein had fetoprotective properties both after intraperitoneal (10 mg/kg) and after intraamniotic (6 and 0.06 micrograms) administration. Ethylnorantifein under similar conditions does not change the action of chloridine, and it prevents the appearance of developmental abnormalities only at the concentration of 0.06 microgram/embryo. These data are discussed in connection with different effects of antifein derivatives on chromatin proteinkinase, which phosphorylates HMG nonhistone proteins.


Assuntos
Anormalidades Induzidas por Medicamentos/prevenção & controle , Embrião de Mamíferos/efeitos dos fármacos , Etimizol/análogos & derivados , Imidazóis/uso terapêutico , Pirimetamina/toxicidade , Teratógenos/toxicidade , Anormalidades Induzidas por Medicamentos/etiologia , Animais , Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Perda do Embrião/induzido quimicamente , Perda do Embrião/prevenção & controle , Etimizol/uso terapêutico , Feminino , Masculino , Gravidez , Ratos
8.
Artigo em Russo | MEDLINE | ID: mdl-9381807

RESUMO

The dynamics of changes in some components of the calcium-regulated system of cortical and hippocampal neurons under the influence of long-term memory enhancers (ethylnorantifein and its analogues M1 and M2) was studied in rat brain. No change was found in the activity of transport Mg, Ca-ATPase and actomyosin-like Ca-ATPase in synaptic membranes 5, 15, 60, and 180 min after the injection of memory enhancers. The activation of the RNA transcription (60 min after the injection) was accompanied by an appreciable increase in activity of the chromatin Ca-ATPase. The amplification of synaptosomal protein synthesis (180 min) was accompanied by an increase in the activation of protein kinase C of synaptic membranes. The increase in Ca-ATPase activity of chromatin was also shown during the consolidation of the conditioned active avoidance in rats. The increase in the activity of protein kinase C seems to be connected with secondary rearrangement in synaptic membranes. The role in the long-term memory is discussed of direct activation of the genetic apparatus by neuroactive substances.


Assuntos
Cálcio/fisiologia , Memória/fisiologia , Neurônios/fisiologia , Animais , ATPases Transportadoras de Cálcio/efeitos dos fármacos , ATPases Transportadoras de Cálcio/fisiologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiologia , Cromatina/efeitos dos fármacos , Cromatina/fisiologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Etimizol/análogos & derivados , Etimizol/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Masculino , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Proteína Quinase C/efeitos dos fármacos , Proteína Quinase C/fisiologia , Ratos , Estimulação Química , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/fisiologia , Fatores de Tempo
11.
Xenobiotica ; 26(9): 935-46, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8893040

RESUMO

1. The disposition of tacrine 1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate (THA, Cognex), was studied using livers obtained from control, phenobarbital (PB), isosafrole (ISO), and 3-methycholanthrene (3-MC) treated rats. 2. Pretreatment of rats with PB, ISO, and 3-MC reduced AUC(10-120 min) of THA in liver perfusates by 28, 32, and 86% respectively. 3. Elimination of [14C]-THA-derived radioactivity into bile was 7.6 +/- 1.2%, 11.7 +/- 2.9%, 14.8 +/- 2.0%, and 46.3 +/- 9.7% (mean +/- SD) of the infusion dose for control PB, ISO, and 3-MC pretreated isolated perfused rat livers, respectively. 4. In perfusion experiments using 3-MC pretreated livers, a marked increase in irreversible protein binding of 3-, 7-, and 8-fold was observed to microsomal, cytosolic and total liver proteins, respectively, compared to control. Only a slight effect was observed on protein binding in perfusion experiments using PB and ISO pretreated animals. 5. Co-incubations of [14C]-THA with the metabolic inhibitors enoxacin, ethimizol, and furafylline in hepatocyte preparations obtained from 3-MC pretreated rats markedly inhibited THA-derived irreversible protein binding. Furafylline, a specific inhibitor of cytochrome P4501A2, had the greatest inhibitory effect (approximately 70%). 6. These results are consistent with a major role of cytochrome P4501A in the metabolism and irreversible protein binding of THA in rat liver and demonstrate the utility of isolated liver perfusion and hepatocyte models for examining the effect of metabolic modulators.


Assuntos
Inibidores da Colinesterase/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Tacrina/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Enoxacino/farmacologia , Indução Enzimática , Etimizol/farmacologia , Glucuronidase/metabolismo , Glutationa/farmacologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Metilcolantreno/farmacologia , Ratos , Ratos Wistar , Teofilina/análogos & derivados , Teofilina/farmacologia
13.
Sud Med Ekspert ; 38(4): 27-9, 1995.
Artigo em Russo | MEDLINE | ID: mdl-8848799

RESUMO

A method for spectrophotometric measurement of metronidasole and ethymisole jointly present in the urine has been developed. Combined polynomes have been designed to eliminate the effects of light-absorbing admixtures extracted from the urine on the results of analysis.


Assuntos
Etimizol/urina , Metronidazol/urina , Espectrofotometria Ultravioleta/métodos , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Delgada , Humanos , Concentração de Íons de Hidrogênio , Espectrofotometria Ultravioleta/estatística & dados numéricos
14.
Eksp Klin Farmakol ; 58(3): 40-2, 1995.
Artigo em Russo | MEDLINE | ID: mdl-7663295

RESUMO

The study was undertaken to reveal the effects of ethymisole on the functional status of blood coagulation and fibrinolytic systems, the body's adaptative reserves of workers from expeditionary-duty teams. Ethymisole was found to normalize the functional status of blood coagulation and fibrinolytic systems, to restore conjunction of their functioning. The use of the drug was ascertained to normalize the activity of lipid peroxidation products, to enhance the adaptative reserves of expeditionary-duty workers by prolonging the resistance phase. It is concluded that ethymisole may be used as an agent that enhances the body's adaptative reserves.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Clima Frio , Etimizol/farmacologia , Fibrinólise/efeitos dos fármacos , Petróleo , Adaptação Fisiológica/efeitos dos fármacos , Adulto , Etimizol/administração & dosagem , Humanos , Imunidade Inata/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Sibéria , Fatores de Tempo
15.
Vopr Med Khim ; 41(1): 27-9, 1995.
Artigo em Russo | MEDLINE | ID: mdl-7771085

RESUMO

Simulation of toxic brain edema-swelling allowed one to analyze the dynamics of blood protein alteration in presence of various neuroleptics. Alterations in blood protein fractions correlated with dynamics of nervous tissue impairments. All the drugs studied exhibited similar antiswelling action involving the gamma-globulin sub-system activation. At the same time, the neuroleptics with activating and depriving effects demonstrated an oppositely directed influence on blood albumins.


Assuntos
Proteínas Sanguíneas/efeitos dos fármacos , Edema Encefálico/fisiopatologia , Etimizol/farmacologia , Metotrimeprazina/farmacologia , Promazina/farmacologia , Animais , Edema Encefálico/induzido quimicamente , Ratos , Ratos Wistar
16.
Ter Arkh ; 67(12): 8-11, 1995.
Artigo em Russo | MEDLINE | ID: mdl-8820044

RESUMO

By the results of bicycle ergometry test 28 coronary heart disease (CHD) patients were divided into 2 groups: with a pronounced anginal syndrome (group 1) and coronary insufficiency evident on ECG (group 2). Vegetative and psychophysiological parameters obtained in the examinees (heart rate, arterial pressure, pain threshold, personality profile) demonstrated that increased pain sensitivity, anxiety, predisposition to neurotic reactions were more typical for patients of group 1. Therapeutic response was achieved after psychophysiological correction by means of creation and activation of artificial stable functional connections of the brain.


Assuntos
Angina Pectoris/psicologia , Isquemia Miocárdica/psicologia , Adulto , Idoso , Angina Pectoris/diagnóstico , Angina Pectoris/tratamento farmacológico , Angina Pectoris/fisiopatologia , Pressão Sanguínea , Fármacos Cardiovasculares/uso terapêutico , Diazepam/uso terapêutico , Quimioterapia Combinada , Eletrocardiografia , Etimizol/uso terapêutico , Teste de Esforço , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/fisiopatologia , Estimulação Luminosa , Psicofisiologia
17.
Lik Sprava ; (7-8): 73-5, 1994.
Artigo em Ucraniano | MEDLINE | ID: mdl-7900360

RESUMO

Aetymizolum was studied for its efficacy in the treatment of patients with osteoarthrosis. The results obtained suggest that aethymizolum is capable of correcting the levels of glycosaminoglucans in the patients' blood serum. With the content of the latter being dependent upon the degree of the articular cartilage destruction in osteoarthrosis deformans, it is suggested that aethymizolum while being endowed with reparative and membrane stabilizing properties may at the same time influence the articular cartilage metabolism and decrease the intensity of the destruction of the later. Effect of aethymizolum is more pronounced in mono-oligoarthrosis and polyosteoarthrosis as well as in stages II and III of the disease course. Conventional therapies (indomethacin, humisolum, Fibs, physiotherapeutic procedures, remedial gymnastics, massage) have no effect on these parameters.


Assuntos
Etimizol/uso terapêutico , Glicosaminoglicanos/sangue , Osteoartrite/tratamento farmacológico , Adulto , Idoso , Terapia Combinada , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/sangue
18.
Eksp Klin Farmakol ; 57(3): 18-20, 1994.
Artigo em Russo | MEDLINE | ID: mdl-8049619

RESUMO

Neurogenic gastric lesions in rats were induced by a combination of immobilization and 3-hour electrostimulation. Neurogenic cardiac injury in rabbits were induced by 3-hour electrical stimulation of the aortic arch. Thereafter the activation of lipid peroxidation in the stomach and heart was recorded. There was an increase in MDA levels and a decrease in antioxidative enzyme activity in the tissues and serum (catalase and superoxide dismutase). The administration of the neurotropic drugs which restore the activity of the sympathetic nervous system (L-DOPA, aethimizol, fenibut and piracetam) was shown to normalize the processes of lipid peroxidation.


Assuntos
Cardiomiopatias/tratamento farmacológico , Mucosa Gástrica/metabolismo , Coração/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Miocárdio/metabolismo , Gastropatias/tratamento farmacológico , Estômago/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Animais , Cardiomiopatias/metabolismo , Avaliação Pré-Clínica de Medicamentos , Etimizol/uso terapêutico , Levodopa/uso terapêutico , Masculino , Piracetam/uso terapêutico , Coelhos , Ratos , Gastropatias/metabolismo , Tranquilizantes/uso terapêutico , Ácido gama-Aminobutírico/análogos & derivados , Ácido gama-Aminobutírico/uso terapêutico
19.
Neurosci Behav Physiol ; 23(5): 404-8, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-7694174

RESUMO

It has been established that an increase in RNA synthesis in the neurons of the cerebral cortex of rats at the stage of consolidation is manifested in well-trained animals more strongly than in poorly trained animals. The selective influence of propylnorantitheine and demethylated derivatives of ethylnorantitheine on the maintenance of conditioned reflexes has been demonstrated. The effects of these substances on consolidation and long-term memory correlate with the change in the RNA-synthesizing activity of neurons during the effect both in systemic experiments and with the direct interaction with the chromatin of the neurons. The participation of the RNA synthesis of cerebral cortical neurons in the mechanisms of long-term memory is discussed.


Assuntos
Condicionamento Clássico/fisiologia , Imidazóis/farmacologia , RNA/biossíntese , Animais , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Condicionamento Clássico/efeitos dos fármacos , Etimizol/farmacologia , Masculino , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos
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