ABSTRACT
In rats with a hemodynamic disorder caused by acute myocardial ischemia, preliminary administration of beditin in a dose of 25 mg/kg fully prevents a manifold increase in the level of 45Ca2+ in the cytosol of brain cells and leads to enhanced trapping and accumulation of labeled calcium in endoplasmic reticulum. With respect to calcium binding in endoplasmic reticulum, the action of beditin substantially differs from that of verapamil.
Subject(s)
Adrenergic alpha-2 Receptor Antagonists , Anticonvulsants/therapeutic use , Brain/metabolism , Calcium Channel Blockers/therapeutic use , Calcium/metabolism , Dioxanes/therapeutic use , Seizures/drug therapy , Thiazoles/therapeutic use , Animals , Endoplasmic Reticulum/metabolism , Mice , Rats , Seizures/etiology , Seizures/metabolism , Species SpecificityABSTRACT
Beditin, or 2-(2-amino-4-thiazolyl)-1,4-benzodioxane hydrochloride, is a new benzodioxane derivative possessing antihypoxant and alpha 2-adrenoreceptor blocker properties. In contrast to idazoxan, a well-known alpha 2-adrenoreceptor blocker, beditin (3 mg/kg) significantly increases the circulation rate and decreases the blood vessel resistance in various brain structures of rats and cats without considerably changing their systemic hemodynamic indices. Upon a one-side ligation of the common carotid artery in rats, beditin prevented a sharp increase in the lactate dehydrogenase activity and a growth in the content of free ammonia in the brain, which are characteristic of the ischemic states. The ammonia-eliminating effect of beditin is related to an increase in the glutamate dehydrogenase activity in the reductive amination reaction.
Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Brain/metabolism , Cerebrovascular Circulation/drug effects , Dioxanes/pharmacology , Receptors, Adrenergic, alpha-2/drug effects , Thiazoles/pharmacology , Animals , Blood Flow Velocity/drug effects , Brain/blood supply , Brain/enzymology , Cats , Glutamate Dehydrogenase/metabolism , Hypoxia/prevention & control , Hypoxia-Ischemia, Brain/metabolism , Hypoxia-Ischemia, Brain/physiopathology , Hypoxia-Ischemia, Brain/prevention & control , L-Lactate Dehydrogenase/metabolism , Male , Muscle, Skeletal/blood supply , Muscle, Skeletal/metabolism , Rats , Rats, Wistar , Skin/blood supply , Skin/metabolism , Vascular Resistance/drug effectsABSTRACT
In experiments on rats with acute myocardial infarction induced by occlusion of the left coronary artery in conscious animals the protective effect of verapamil on the heart, brain, liver, and kidneys in this disease was studied. The effectiveness of the drug was judged by the changes in the 45Ca2+ content in the intracellular structures (cytosol, mitochondria, endoplasmic reticulum) of the organs under study. A single injection of 200 micrograms/kg verapamil in acute myocardial infarction reduces considerably the content of 45Ca2+ in the intracellular structures of these organs and thus prevents the development of pathological processes.
Subject(s)
Calcium Channel Blockers/pharmacology , Calcium/metabolism , Cytosol/drug effects , Endoplasmic Reticulum/drug effects , Mitochondria/drug effects , Myocardial Ischemia/metabolism , Verapamil/pharmacology , Acute Disease , Animals , Calcium Channel Blockers/therapeutic use , Calcium Radioisotopes , Cytosol/metabolism , Disease Models, Animal , Drug Evaluation, Preclinical , Endoplasmic Reticulum/metabolism , Male , Mitochondria/metabolism , Myocardial Ischemia/drug therapy , Rats , Verapamil/therapeutic useABSTRACT
The simulation of the hypo- and hyperactivity of the hypophysis-adrenocortical system induced considerable changes in the reactivity of alpha 2-adrenoceptors, as well as in the resistance of the organism to stressful influences. The findings support the assumption that the blockade of alpha 2-adrenoceptors is one of the key features in the adaptive mechanism of the glycocorticoid hormones action.
