RESUMO
The work is devoted to the use of quantum-pharmacological approaches in pharmacokinetic investigations. The main objective of the pharmacological researches is to find new, more active and less toxic drugs. To date, such a search is carried out empirically. The current approach can not fully meet the needs of medicine in the new drugs, requires considerable time and financial costs and does not meet modern standards of bioethics. Quantum pharmacology leads to the synthesis of drugs with desired properties is much faster and more efficient. Computer prediction of pharmacokinetic and biopharmaceutical properties of biologically active substances can make 50-70% more effective development of original drugs.
Assuntos
Simulação por Computador , Sistema Enzimático do Citocromo P-450/metabolismo , Desenho de Fármacos , Albumina Sérica/química , Animais , Sítios de Ligação , Sistema Enzimático do Citocromo P-450/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Cinética , Modelos Químicos , Ligação Proteica , Relação Quantitativa Estrutura-Atividade , Teoria Quântica , Albumina Sérica/metabolismo , Eletricidade Estática , TermodinâmicaRESUMO
Neurophysiological experiments on anesthetized rats were used to study the effects of various doses (12.5, 25, 37.5 mg/kg, i.v.) of drug composition migrepin (representing a combination of potassium-2,4-dichlorobenzoate, carbamazepine, and caffeine) on background firing of the trigeminal nucleus caudalis neurons and their responses to electrical stimulation of the dura mater. It was found that migrepin produces direct, dose-dependent inhibitory action on functional activity of TNC neurons. The results confirmed anti-migraine properties of the drug but did not exclude the necessity to study its action in clinical trials.
Assuntos
Analgésicos/farmacologia , Dura-Máter/efeitos dos fármacos , Transtornos de Enxaqueca/tratamento farmacológico , Neurônios/efeitos dos fármacos , Núcleo Inferior Caudal do Nervo Trigêmeo/efeitos dos fármacos , Animais , Cafeína/farmacologia , Carbamazepina/farmacologia , Clorobenzoatos/farmacologia , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Dura-Máter/fisiologia , Estimulação Elétrica , Injeções Intravenosas , Masculino , Microeletrodos , Transtornos de Enxaqueca/fisiopatologia , Oscilometria , Potássio/química , Ratos , Ratos Wistar , Núcleo Inferior Caudal do Nervo Trigêmeo/fisiologiaRESUMO
The state of lipid peroxidation and antioxidant system in blood were been studied on the models of skin wound and radioinduced ulcer in rats. It was shown that the healing of skin wound by secondary strength is accompanied by activation of processes lipid peroxidation in plasma and erythrocytes during 15 days. The development of radioinduced ulcer is characterized by more high degree activation of lipid peroxidation beginning with latent period and till forming ulcer (30 days). Only in process of radioinduced ulcer development two phase of activation lipid peroxidation and decrease of antioxidant enzyme activity--catalase and superoxid dismutase--were established. Secondary phase of lipid peroxidation activation was coincided with period of clinical appearances and it was possibly explained by exhaustion of antioxidant system.
Assuntos
Antioxidantes/metabolismo , Eritrócitos/metabolismo , Peroxidação de Lipídeos , Lesões por Radiação/metabolismo , Úlcera Cutânea/metabolismo , Pele/lesões , Animais , Catalase/metabolismo , Eritrócitos/enzimologia , Lipídeos/sangue , Lipoproteínas/sangue , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
By 8-11 enzymes, using polyacrylamide gel electrophoresis, 378 isolates from R. opimus, 3 isolates from M. libycus, 4 isolates from P. andrejevi, 1 isolate from P. papatasi, 1 isolate from S. murgabiensis and 25 isolates from human patients with skin leishmaniasis have been identified. Using starch gel electrophoresis, 17 strains from R. opimus and 3 strains from patients have been additionally identified by 12 enzymes. All the isolates were tested for ability to cause leishmaniasis disturbances in golden hamsters intracutaneously injected into the ear. It is established that L. major is a polytypic group which on the territory of the USSR consists of 3 independent species: L. major (in a narrower sense), L. gerbilli and L. sp. nov, a new earlier unknown species. All three types of Leishmania are specific parasites of R. opimus and only L. major may affect man and M. libycus. 3 types of Leishmania may coexist in the body of one animal. In R. opimus and golden hamsters, all of them caused only skin damages, visceralization was never registered. In golden hamsters, L. major always caused progressing ulcers, while L. sp. nov. and L. gerbilli caused only infiltrative damages. Only 9 (3%) of 268 L. sp. nov. isolates caused ulcers developing similar to those caused by L. major in the experimental animals. The data obtained account for the local nature and seasonal regularities of the epidemic process in the natural foci of skin leishmaniasis by the changing proportion of L. major in the complex of Leishmania encountered in R. opimus.