RESUMEN
A series of alpha-asarone isomers was synthesized and investigated for their hypolipidemic and antiplatelet activity. Considering the hypolipidemic activity in rats at a dose of 80 mg/kg/day, some isomers were more potent than clofibrate at 150 mg/kg. Compound 3 was one of the most active agents elevating the HDL cholesterol level by 56% and lowering the LDL cholesterol level by 46.8% in rats after 7 days of administration. The activities of the platelet aggregation test in vitro were significant but lower than those of the reference substances (indomethacine and acetylsalicylic acid). In the pulmonary thromboembolic in vivo test in mice, two compounds (alpha-asarone (6) and compound 4) produced significant antithrombotic effects at 100 mg/kg, namely 44% and 52% protection against lung microembolia, respectively. alpha-Asarone derivatives form a new group of potential hypolipidemic and/or antithrombotic agents. The compounds 3, 4, and 6 may serve as lead substances whose structural modifications may result in original drugs.
Asunto(s)
Anisoles/síntesis química , Fibrinolíticos/síntesis química , Hipolipemiantes/síntesis química , Derivados de Alilbenceno , Animales , Anisoles/química , Anisoles/farmacología , Fibrinolíticos/química , Fibrinolíticos/farmacología , Humanos , Hipolipemiantes/química , Hipolipemiantes/farmacología , Técnicas In Vitro , Pulmón/irrigación sanguínea , Masculino , Ratones , Agregación Plaquetaria/efectos de los fármacos , Ratas , Ratas Wistar , Estereoisomerismo , Relación Estructura-Actividad , Tromboembolia/prevención & controlRESUMEN
PURPOSE: Analysis of local and systemic effects of RS-timolol enantiomer and S-timolol in patients with ocular hypertension and glaucoma: evaluation of Risk/Benefit Ratio. MATERIAL AND METHODS: 19 patients (38 eyes) receiving 0.85% RS-timolol and 10 patients (20 eyes) receiving 0.5% S-timolol were evaluated using a double-blank test. Intraocular pressure, heart rate, systemic arterial blood pressure, ECG and spirometry were recorded before and 2 hours after drugs administration and after 7 days of treatment. RESULTS: There were no statistically significant differences between intraocular pressure-lowering effects of RS-timolol and S-timolol. In patients receiving both medicines bradycardia was detected 2 hours after drugs administration. Patients receiving RS-timolol showed increased expiratory capacity in comparison to those receiving S-timolol. There was no detectable influence of both medicines on ECG and systemic arterial blood pressure. CONCLUSIONS: 0.85% RS-timolol and 0.5% S-timolol produced comparable intraocular pressure-lowering effects. 0.85% RS-timolol exerted less severe influence on respiratory system.