RESUMO
The pharmacokinetic study of a new original antipsychotic drug Dilept in healthy volunteers was performed. Volunteers received Dilept as single 20, 40 or 60 mg tablets. The parent drug in the human blood plasma was detected in low concentrations and short-term time due to intensive biotransformation with formation of two metabolites N-caproyl-L-prolyl-tyrosin (M-1) and N-caproyl-L-prolin (M-2). After 20 and 40 mg of Dilept parent drug was detected in certain time points and after 60 mg for 1 h. M-1 and M-2 metabolites were registered in the blood plasma for 4 - 8 h. Theirs concentrations were 10 - 100 times higher of unchanged drug ones. Metabolites pharmacokinetics in the studied dosage range was nonlinear.
Assuntos
Antipsicóticos/farmacocinética , Prolina/análogos & derivados , Tirosina/análogos & derivados , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/sangue , Área Sob a Curva , Biotransformação , Esquema de Medicação , Humanos , Masculino , Prolina/administração & dosagem , Prolina/sangue , Prolina/farmacocinética , Comprimidos , Tirosina/administração & dosagem , Tirosina/sangue , Tirosina/farmacocinéticaRESUMO
The study was focused on the clinico-pharmacological analysis of differences between subjective and objective assessment of the effects of antiasthenic drug ladasten and placebo effects in patients with neurasthenia with different individual patterns manifested in their EEG alpha rhythms and MMPI findings. It is established that, in patients with neurasthenia characterized by reduced EEG alpha activity combined with emotional lability and inertness, the therapeutic action and effectiveness of ladasten and placebo was more robust (the subjective estimation was higher) than in patients with prominent alpha rhythm and sthenic personal traits. The self-assessment of the effect of single test doses of ladasten and placebo was independent of the individual differences of EEG alpha rhythm organization and personal traits with respect to tolerability, wish to continue the treatment, activating and calming effects. In long-term treatment, higher subjective estimations of the ladasten and placebo effect appeared in patients with reduced EEG alpha rhythm, and the difference corresponded to objective indices of the psychotropic action and effectiveness of the drug.
Assuntos
Adamantano/análogos & derivados , Ritmo alfa/efeitos dos fármacos , Neurastenia/tratamento farmacológico , Psicotrópicos/uso terapêutico , Adamantano/uso terapêutico , Adolescente , Adulto , Autoavaliação Diagnóstica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurastenia/fisiopatologia , Efeito Placebo , Psicotrópicos/farmacologiaRESUMO
Differences between phenazepam formulations were found in the clinical study of drug effects on the psychophysiological state in patients with anxiety disorder. Phenazepam did not cause negative changes of psychophysiological parameters. In patients with anxiety disorders, the most significant positive therapeutic actionon psychophysiological state was observed in the case of using transdermal phenazepam formulation.
Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/psicologia , Atenção/efeitos dos fármacos , Benzodiazepinas , Administração Cutânea , Adolescente , Adulto , Transtornos de Ansiedade/fisiopatologia , Atenção/fisiologia , Benzodiazepinas/uso terapêutico , Formas de Dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacos , Análise e Desempenho de TarefasRESUMO
Self-evaluation of the effect of single-dose (15 mg) ladasten administration versus placebo has been studied in patients with neurasthenia diagnosis. Relationships between self-evaluation parameters and personal features, psychopathological and psychophysiological parameters of patients, drug action characteristics, and course treatment effectiveness have been analyzed. Results suggest that the self-rated high tolerability of ladasten treatment is comparable with that of placebo. No relationships are found between the self-evaluated single-dose effects of ladasten and personal features of patients. Correlations of the self-estimations and some psychopathological and psychophysiological parameters before treatment, main drug effects, and overall course treatment effectiveness are revealed, whereas the self-evaluation of placebo effect was related to personal features.
Assuntos
Adamantano/análogos & derivados , Afeto/efeitos dos fármacos , Ansiolíticos/uso terapêutico , Atividade Motora/efeitos dos fármacos , Neurastenia/tratamento farmacológico , Adamantano/administração & dosagem , Adamantano/uso terapêutico , Administração Oral , Adulto , Ansiolíticos/administração & dosagem , Autoavaliação Diagnóstica , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurastenia/diagnóstico , Neurastenia/fisiopatologia , Exame Físico , Efeito Placebo , Psicofisiologia , Projetos de Pesquisa , Distúrbios do Início e da Manutenção do Sono , Fases do Sono , Resultado do TratamentoRESUMO
Self-evaluation of single-dose (15 mg) action and course treatment (30 mg daily) results were studied in patients with anxiety and asthenic disorders treated with the new anxiolytic afobazole. Also, relationships between self-evaluated parameters and personal features, clinician-rated therapeutic changes, and treatment effectiveness were analyzed. The study was conducted according to formalized protocol using standard scales and methods. Results suggest that higher self-rated tolerability and patient acceptability were associated with afobazole treatment in comparison to benzodiazepines. The results revealed relationships between self-evaluated single-dose effects of afobazole and other parameters, personal features, cognitive impairments severity, main drug effects, and overall treatment effectiveness.
Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Astenia/tratamento farmacológico , Benzimidazóis/uso terapêutico , Autoavaliação Diagnóstica , Morfolinas/uso terapêutico , Adolescente , Adulto , Ansiolíticos/administração & dosagem , Ansiedade/psicologia , Astenia/psicologia , Benzimidazóis/administração & dosagem , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Testes Neuropsicológicos , Cooperação do Paciente , Satisfação do Paciente , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
Clinical investigation of a transdermal phenazepam preparation (phenapercuten) in patients diagnosed with different anxiety disorders revealed an original therapeutic action of the new drug, which included both a selective anxiolytic effect and an activating (antiasthenic) component in the absence of undesired sedative and miorelaxant properties. It is shown that the specific action of phenapercuten is related to features of the pharmacokinetic profile of this transdermal drug that is characterized by a low levels of active compound in the blood plasma and by the absence of peak concentrations. TTS Phenapercuten was most effective in patients with anxiety disorders of simple structure.
Assuntos
Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Benzodiazepinas/uso terapêutico , Administração Cutânea , Adolescente , Adulto , Ansiolíticos/administração & dosagem , Ansiolíticos/efeitos adversos , Ansiolíticos/farmacocinética , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Benzodiazepinas/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Clinical and electroencephalographic (EEG) analysis ofladasten action in anxiety-asthenic patients with respect to their EEG-defined individual typological characteristics was carried out. Primary psychopathologic disorders and ladasten effects were assessed by objective classification methods (factor and cluster analyses), and individual EEG types characterized by marked or reduced alpha rhythm were determined. No significant correlations between baseline EEG results and the initial mental condition indices were found. Significant differences ofladasten action in patients with different EEG types were found. It was established that, in patients with marked alpha rhythm corresponding to asthenic personal traits, ladasten exhibits predominantly a psychostimulant action assessed by clinical rating scales, which is accompanied by high frequencies of alpha rhythm increase and beta 1 and beta 2 rhythms decrease. In patients with reduced alpha rhythm and the EEG type corresponding to asthenic personal traits, ladasten action was characterized by an increase of alpha-rhythm low frequencies and the opposite reaction of beta 1 and beta 2 rhythms, whose are typical for the EEG pattern of anxiolytic effect. These results may indicate that the effect of ladasten depends on the initial brain activity level, which varies in patients with different individual typological traits.
Assuntos
Adamantano/análogos & derivados , Neurastenia/tratamento farmacológico , Adamantano/uso terapêutico , Adolescente , Adulto , Ritmo alfa/métodos , Ritmo beta/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurastenia/fisiopatologiaRESUMO
The psychotropic actibn and efficacy of ladasten, a new psychostimulant with anxiolitic activity, was studied in a standard clinical trial involving therapy of patients with psychogenic asthenic disorder. Ladasten exhibits a unique combination of therapeutically significant stimulant and anxiolytic effects, which is unusual of psychostimulants. At the same time, the results of ladasten action upon single administration on the dynamics of psychopatological disorders and psychological self-test indexes show that the psychostimulant action is predominating. The established combination of the psychostimulant and anxiolytic effects of ladasten is optimal for the therapy of patients with psychogenic asthenic disorders. Ladasten shows high efficacy in the treatment of these disorders testify and has good prospects for practical application.
Assuntos
Adamantano/análogos & derivados , Ansiolíticos/uso terapêutico , Astenia/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Adamantano/administração & dosagem , Adamantano/uso terapêutico , Adolescente , Adulto , Ansiolíticos/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
Among 140 patients with psychogenically induced depressive states first developing in old age the author identified a group of patients (n = 33) whose clinical picture of depressive disturbances was determined by a combination of reactive and endogenic features and corresponded to the description of the so-called endoreactive depressions. Four successive stages in their development are described. On the basis of analysis of the mechanisms of the development of these depressions, their clinico-psychopathologic structure, follow-up and constitutional-genetic data, these diseases have been referred to borderline forms of manic-depressive psychosis. It is suggested that the premorbid structure of the personality of the studied patients is the expression of the constitutional-genetic predisposition for affective disturbances while its premanifest time-course may be considered as a latent stage of the disease development.
Assuntos
Transtornos de Adaptação/diagnóstico , Transtorno Bipolar/diagnóstico , Transtorno Depressivo/diagnóstico , Transtornos de Adaptação/etiologia , Transtornos de Adaptação/psicologia , Idoso , Transtorno Bipolar/etiologia , Transtorno Bipolar/psicologia , Doença Crônica , Transtorno Depressivo/etiologia , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Personalidade , PsicopatologiaRESUMO
Atropine-comatose therapy was performed in 18 patients with schizophrenia and disorders in the framework of an obsessive-syndrome. Improvement was seen in 11 of the 18 patients. A psychopathological analysis of obsessive disorders in this group of patients demonstrated that they were characterized by manifold traits, instability, abstract content of obsessions, a tendency towards their complication and expansion of obsessional disturbances. The absence of any effect was seen in 7 of the cases. They were characterized by montony, monomorphism, everday content and by their structure were near to constitutionally conditioned psychasthenic doubtfulness.
Assuntos
Atropina/uso terapêutico , Comportamento Compulsivo/terapia , Comportamento Obsessivo/terapia , Esquizofrenia/terapia , Coma/induzido quimicamente , Feminino , Humanos , Masculino , Psicopatologia , SíndromeRESUMO
The paper describes premorbid features of patients with late endogenous depressions and presents relevant genealogical data. Schizophrenic psychoses which were constantly found in these families were most thoroughly studied. These studies demonstrated intrafamial similarities of mental disorders, despite the presence of different disease entities in probands and their relatives with schizophrenia. The assumption is made on the affinity of some of the studied late endogenous psychoses to a constitutional-genetic predisposition to schizophrenia.
Assuntos
Depressão/genética , Esquizofrenia/genética , Transtornos Psicóticos Afetivos/genética , Fatores Etários , Idoso , Transtorno Bipolar/genética , Constituição Corporal , Depressão/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Periodicidade , Personalidade , Transtorno da Personalidade Esquizoide/genética , Esquizofrenia/diagnóstico , SíndromeRESUMO
The intensity of lipid peroxidation was studied in schizophrenic and manic-depressive patients. Peroxidation was found to be activated in these diseases as assessed by the content of peroxidation products in the lipid fraction of blood plasma. Manic-depressive patients showed a significant decrease in the intensity of peroxidation processes with improvement in the clinical symptoms of the disease.
Assuntos
Transtorno Bipolar/sangue , Peróxidos Lipídicos/sangue , Bases de Schiff/sangue , Esquizofrenia/sangue , Adolescente , Adulto , Feminino , Fluorometria , Humanos , Masculino , Pessoa de Meia-Idade , PolarografiaRESUMO
A standard clinical trial including pharmaco-EEG investigation of the new selective anxiolytic afobazole was performed on a group of 30 patients with anxiety and anxious-asthenic disorders and premorbid individual asthenic profile traits. Afobazole exhibits the anxiolytic action with an activating component in the absence of sedative and myorelaxant effects. The clinical trial results confirmed good prospects of using the experimentally validated pharmacogenetic concept of anxioselectivity as a methodological approach to the design of new drugs possessing selective anxiolytic properties.
Assuntos
Ansiolíticos/uso terapêutico , Benzimidazóis/uso terapêutico , Morfolinas/uso terapêutico , Adolescente , Adulto , Ansiolíticos/efeitos adversos , Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Ansiedade/psicologia , Benzimidazóis/efeitos adversos , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/efeitos adversos , Neurastenia/tratamento farmacológico , Neurastenia/fisiopatologia , Neurastenia/psicologia , Estresse Psicológico/psicologiaRESUMO
A clinical pharmacological 56-day trial was devoted to the effect of tanakan on the psychophysiological state of 26 patients with psychogenic and post-traumatic asthenic disorders. The drug was found to produce a positive effect on the psychophysiological state, with most pronounced improvement in the attention characteristics, short-term visual memory, operational component, and integral operator performance index. The results confirmed the positive action of tanakan on the cognitive and mnestic functions, which is analogous to the effect of nootropes. The antiasthenic, anxiolytic, antiamnesic, and vegetotropic components in the pharmacological spectrum of tanakan correlate with the positive psychophysiological effects. It is shown that positive changes in the psychophysiological state play an important role in the complex therapeutic action of tanakan in the treatment of asthenic disorders.
Assuntos
Astenia/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Adolescente , Adulto , Astenia/etiologia , Astenia/psicologia , Transtorno da Personalidade Borderline/complicações , Feminino , Ginkgo biloba , Humanos , Masculino , Pessoa de Meia-Idade , Ferimentos e Lesões/complicaçõesRESUMO
The effect of placebo and gidazepam on the state, psychophysiological predictors of the quality of the operator's performance and its results in individuals with neurotic reactions was studied (test dose 20 mg 7-day course, 40 mg daily, 24 individuals), as well as the effect of gidazepam and phenazepam (42 individuals with neurotic and neurosis-like states; gidazepam test doses 20 and 50 mg, 14-day course, 40 and 100 mg daily; phenazepam test doses 0.5 and 1 mg, 14-day course, daily dose 2 mg). The generally accepted methods of clinical and psychophysiological examination were applied. Gidazepam in the doses under study did not yield to phenazepam in therapeutic activity. A single and a course administration of gidazepam improved the parameters of the psychophysiological state and the efficacy of the operator performance in patients with neurotic reactions and in those with neurotic and neurosis-like states. This makes it possible, whenever necessary, to recommend this drug for the treatment of the indicated disorders in the working operators.
Assuntos
Ansiolíticos/uso terapêutico , Benzodiazepinas , Benzodiazepinonas/uso terapêutico , Militares/psicologia , Transtornos Neuróticos/tratamento farmacológico , Desempenho Psicomotor/efeitos dos fármacos , Adulto , Ansiolíticos/farmacologia , Benzodiazepinonas/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Transtornos Neuróticos/fisiopatologia , Transtornos Neuróticos/psicologia , Psicopatologia , Psicofisiologia , Federação Russa , Fatores de TempoRESUMO
The spectral-coherence analysis of phenazepam single-dose action in patients with anxiety disorder was performed. Significant changes in coherence parameters indicating the generalized character of reorganizations of interzonal connections with the involvement of delta, alpha, theta and beta-1 to beta-3 rhythms, including both their strengthening and weakening, were revealed. Correlations between the character of reorganizations of interzonal relations and subjective assessments of the drug effect were observed: activating and antianxiety drug effects were correlated with tolerability and the wish to continue treatment with the drug. Results suggest that drug effect on EEG spectra is more informative when subjective assessments are taken into account.
Assuntos
Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Benzodiazepinas/administração & dosagem , Encéfalo/efeitos dos fármacos , Eletroencefalografia , Senso de Coerência/efeitos dos fármacos , Adulto , Encéfalo/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
An aim of a randomized blind study was to assess therapeutic efficacy and safety of ladasten used as an antiastenic drug in patients with neurasthenia. Tasks of the study included the investigation of characteristics of therapeutical actions, efficacy of the drug comparing to placebo, possible side-effects and probability of the development of "withdrawal syndromes". The design of the study included a wash-out period, a monotherapy with ladasten and placebo during 28 days and a final 1-week period of receiving placebo. Standartisized objective and subjective methods of mental state evaluation in patients were administered. The results obtained suggest that a combination of psychostimulant and anxiolytic actions in the spectrum of psychotropic activity of ladasten determines the its high therapeutic efficacy in asthenic disorders. It has been found that ladasten is superior in the rate and degree of reduction of main symptoms of asthenic syndrome compared to placebo. The absence of "withdrawal syndrome" after the drug withdrawal reveals the lack of addictive potential in this drug.
Assuntos
Adamantano/análogos & derivados , Ansiolíticos/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Neurastenia/tratamento farmacológico , Adamantano/administração & dosagem , Adamantano/uso terapêutico , Ansiolíticos/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Humanos , Neurastenia/diagnóstico , Placebos , Fatores de Tempo , Resultado do TratamentoRESUMO
An effect of a new nootropic drug noopept on the dynamics of main EEG rhythms and narrow-band spectral EEG characteristics in patients with cerebral asthenic and cognitive disturbances caused by traumas or vascular brain diseases has been studied. Noopept caused the EEG changes characteristic of the action of nootropics: the increase of alpha- and beta-rhythms power and reduction of delta-rhythms power. The reaction of alpha-rhythm was provided mostly by the dynamics of its low and medium frequencies (6,7-10,2 Hz), the changes of beta-rhythm were augmented in frontal and attenuated in occipital areas. The analysis of frequency and spatial structure of EEG changes reveals that noopept exerts a nonspecific activation and anxyolytic effect. The differences in EEG changes depending on the brain pathology were found. The EEG indices of nootropic effect of the drug were most obvious in cerebral vascular diseases. The EEG changes in posttraumatic brain lesion were less typical.
Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Transtornos Cognitivos , Dipeptídeos/farmacologia , Dipeptídeos/uso terapêutico , Eletroencefalografia/efeitos dos fármacos , Nootrópicos/farmacologia , Nootrópicos/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto , Circulação Cerebrovascular/efeitos dos fármacos , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Testes Neuropsicológicos , Índice de Gravidade de DoençaRESUMO
Sixty-two patients with generalized anxiety disorder (GAD) and neurasthenia were studied. The effect of selank (30 patients) was compared to that of medazepam (32 patients). Patient's state was assessed with psychometric scales (Hamilton, Zung, CGI). Enkephalin activity in the blood serum was measured as well. The anxiolytic effects of both drugs were similar but selank had also antiasthenic and psychostimulant effects. The clinical-biological study revealed that patients with GAD and neurasthenia had the decreased level of tau(1/2) leu-enkephalin which was correlated with disease duration, severity of symptoms related to anxiety and asthenia and autonomic disorders. The increase of this parameter and stronger positive correlations with anxiety level were observed during the treatment with selank mostly in patients with GAD.
Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Neurastenia/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Administração Intranasal , Administração Oral , Adolescente , Adulto , Ansiolíticos/administração & dosagem , Ansiolíticos/farmacocinética , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/psicologia , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Encefalinas/sangue , Feminino , Seguimentos , Humanos , Masculino , Medazepam/administração & dosagem , Medazepam/farmacocinética , Pessoa de Meia-Idade , Neurastenia/sangue , Neurastenia/psicologia , Oligopeptídeos/farmacocinética , Psicometria/métodos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
A standardized clinical and pharmacological trial of the peculiarities of action and efficacy of aphobazol, a new anxyolytic with non-benzodiazepine structure, has been conducted. An effect of the drug on different anxiety disorders has been studied. It is shown that combined anxyolytic and activating action exerted the main effect. The best efficacy of aphobazol was found in anxiety disorders of "simple" structure. In more complicated anxiety disorders, aphobazol efficacy depended on the correlation between clinical appearances of deeper registers and anxiety affect. The best results have been achieved in patients with acute anxiety-phobic disorders, in the structure of which sensible anxiety with episodes of generalization, dominating vivid ideas, sensibly saturated phobias with pronounced autonomic disorders and senestalgias prevailed. In case of chronic disease course, with formation of more inert, "complex" in structure and deep by register psychopathological disorders (cognitive character of anxiety, appearances of agoraphobia and avoidance behavior, heteronomous body sensations and hypochondriac activity), the efficacy of aphobazol treatment was significantly lower. In this case a therapy combined with selective inhibitors of serotonin reuptake and neuroleptics is needed.