RESUMEN
Cerebrovascular diseases (CVDs) are one of the leading causes of death and disability In Russia: they rank second in the structure of mortality from diseases of the circulatory system and in the overall mortality of the population. Successful treatment of CVD involves an integrated approach to the problem, taking into account the compensation of cardiovascular disorders, the elimination of neurological and psychopathological syndromes, the improvement of cerebral circulation and the use of neuroprotective agents that increase the resistance of brain tissue to hypoxia and ischemia. Insufficient clinical efficacy of neuroprotectors is due to a number of objective reasons, of which only two are universal. The first of these reasons is the timing of the start of therapy in the clinic, as a rule, is outside the «therapeutic window¼; the second reason is the fact that disturbance of the patency of the cerebral vessels in the affected area makes it difficult or impossible to deliver the drug to the penumbra area. The way out of this situation is the intranasal route of drug administration, which is characteristic for the analogs of regulatory peptides such as for H-Met-Glu-His-Phe-Pro-Gly-Pro-OH (MGHPPGP). The review of clinical studies indicates that MGHPPGP is clinically effective in the treatment of ischemic stroke both in the acute period of stroke and in the recovery period. The clinical efficacy of MGHPPGP was shown both in atherothrombotic and cardioembolic subtypes of stroke, against the background of blood flow disturbances in both the carotid and vertebrobasilar systems.
Asunto(s)
Accidente Cerebrovascular Isquémico , Fármacos Neuroprotectores , Oligopéptidos , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Oligopéptidos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/administración & dosificación , Rehabilitación de Accidente Cerebrovascular/métodos , Administración IntranasalRESUMEN
Selective blocking of individual isoforms of carbonic anhydrase (CA) is now one of the main directions in the development of its inhibitors. The new 1,2,4-oxadiazole-containing sulfonamides B12 and B13 predominantly block CA II and CA IX. The study of acute toxicity of B12 and B13 showed their safety. Substance B13 caused a relatively short-term, but rapid (within 30 min) decrease in the intraocular pressure in rabbits, which indicates the promise of its use for the emergency decrease in the intraocular pressure in medical practice. Analysis of the effects of sulfonamides on the functions of CNS showed that compound B12 probably exhibit tranquilizing activity; B13 is promising for the creation of drugs that have an antidepressant effect and at the same time increase the mental and physical performance.
Asunto(s)
Anhidrasas Carbónicas , Animales , Conejos , Anhidrasas Carbónicas/metabolismo , Inhibidores de Anhidrasa Carbónica/farmacología , Relación Estructura-Actividad , Sulfonamidas/farmacología , Antígenos de Neoplasias , Isoformas de ProteínasRESUMEN
The work was aimed at assessing in vivo the analgesic properties of ten decahydroquinoline derivatives (pharmacologically active substances, PAS) and deter- mining the role of opioid receptors in mechanism of their action. Among the derivatives studied, pronounced analgesic properties at a dose of 1/4 LD50 was ob- served for two compounds (PAS-70 and PAS-71), while four compounds (PAS-66, PAS-69, PAS-74, PAS-76) produced weak and short anesthetic effects. PAS-70 and PAS-71 showed analgesic action even in a dose of 1/8 LD50. The maximum effect of PAS-70 and PAS-71 was developed within 20 - 60 min after administration and lasted for two hours (PAS-70 in a dose of 1/4 LD50, PAS-71 in doses of 1/4 and 1/8 LD50). The analgesic effect of PAS-70 (at 1/4 LD5,) and PAS-71 (at 1/4 and 1/8 LD50) significantly exceeds that of reference drugs metamizol (1/4 LD5) and ketorolac (1/4 LD50). The mechanism of drug action is not related to opioid receptors.
Asunto(s)
Analgésicos no Narcóticos/farmacología , Umbral del Dolor/efectos de los fármacos , Quinolinas/farmacología , Analgésicos no Narcóticos/química , Animales , Relación Dosis-Respuesta a Droga , Femenino , Dosificación Letal Mediana , Masculino , Ratones , Quinolinas/química , Tiempo de Reacción/efectos de los fármacosRESUMEN
Retrospective analysis included case histories of 182 patients with hypertensive disorders and one or more crises (HC). The aim was to study the relationship between drug therapy and occurrence of HC. As known, clinical diagnosis of hypertensive disorder dictates therapeutic strategy for AH. It was shown that diagnosis of neurocirculary dystonia (asthenia) prevented timely prescription antihypertensive treatment and resulted in HC. Mathematical simulation of anti-AH therapy in the presence of HC allows patients at high risk of stroke to be identified for follow-up and adequate treatment.