ABSTRACT
In chronic experiments in rabbits, foridone, 0.3 mg/kg, i.v., caused a significant increase in overall and local cerebral circulation and pO2 in various brain regions. In conscious rats, foridone given in the same dose under 30-min carotid occlusion resulted in a less profound decrease in brain blood supply to the baseline level during recirculation and prevented disturbances in oxidative processes in brain tissue and development of brain edema.
Subject(s)
Calcium Channel Blockers/pharmacology , Cerebrovascular Circulation/drug effects , Nifedipine/analogs & derivatives , Animals , Brain/drug effects , Brain/metabolism , Drug Evaluation, Preclinical , Ischemic Attack, Transient/drug therapy , Ischemic Attack, Transient/physiopathology , Male , Nifedipine/pharmacology , Oxygen Consumption/drug effects , Partial Pressure , Rabbits , Rats , Time FactorsABSTRACT
In experiments on anesthetized cats, foridone (1 and 3 micrograms/kg/min intravenously) was found to increase cerebral blood flow by 6-26% with a moderate decrease of systemic arterial blood pressure indicating that the drug possessed properties with respect to a selective cerebral vasodilatator. Phenygidine (0.3-3 micrograms/kg/min) did not exhibit such a property. Intravenous administration of foridone (1 microgram/kg/min) to cats one day after intracerebral hemorrhage produced a significant improvement of blood supply to the brain, glucose utilization by the brain, a moderate increase of oxygen consumption.
Subject(s)
Antihypertensive Agents/pharmacology , Cerebral Hemorrhage/drug therapy , Cerebrovascular Circulation/drug effects , Nifedipine/analogs & derivatives , Acid-Base Equilibrium/drug effects , Animals , Antihypertensive Agents/therapeutic use , Blood Gas Analysis , Blood Pressure/drug effects , Carbohydrate Metabolism , Cats , Cerebral Hemorrhage/physiopathology , Female , Glucose/metabolism , Hemodynamics/drug effects , Infusions, Intravenous , Male , Nifedipine/administration & dosage , Nifedipine/pharmacology , Nifedipine/therapeutic use , Oxygen Consumption/drug effectsABSTRACT
Using the radioisotope method, the Ca2+ transport through proteoliposomes was investigated. The proteoliposomes originating from total brain lipids and skeletal muscle T-system membranes of the rabbit were shown to possess a Ca2+ permeability which can be stimulated by 1.4-dihydroxypyridine derivatives (10(-9)-10(-7) M). Verapamil and Cd2+ (10(-5) M and 10(-3) M, respectively) inhibit the Ca2+ permeability of proteoliposomes stimulated by dihydroxypyridine derivatives. The activating effect of the latter depends on the microviscosity of the proteoliposome lipid bilayer. An addition of cholesterol to brain phospholipids at a ratio of 1:5 increases the stimulating effect of dihydroxypyridine by 50%.
Subject(s)
Calcium Channel Blockers/pharmacology , Calcium/metabolism , Muscles/metabolism , Proteolipids/metabolism , Animals , Biological Transport/drug effects , Brain Chemistry , Cadmium/pharmacology , Dihydropyridines/pharmacology , In Vitro Techniques , Membranes/metabolism , Permeability , RabbitsABSTRACT
A novel effective antihypertensive agent, 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl++ +)-1,4-dihydropyridine (ryodipine, PP-1466) has been obtained. A method for ryosidine synthesis has been developed, side products of PP-1466 synthesis have been isolated and identified. Special characteristics (IRS, UVS, NMR, MS) and chromatography data (TLC, HPLC) are cited.
