On the mechanism of action of the antianginal drug nonachlazine on ischemic myocardium. 1983

N V Kaverina, and A I Turilova, and Rozonov YuB, and T N Azvolinskaya, and S A Kryzhanovsky

The activity of a new antianginal drug, nonachlazine, synthetized in the Institute of Pharmacology, Academy of Medical Sciences of the USSR, has been demonstrated using model myocardial ischemias on anesthetized dogs and conscious cats. Antianginal activity was evaluated by ECG, epicardial electrogram, lactate level, and lactate/pyruvate ratio in the venous blood flowing from the ischemic myocardial area. The study of the cardiotropic effect of nonachlazine provided the following findings: (1) nonachlazine enhances ino- and chronotropic functions of the heart via stimulation of its beta-adrenergic receptors; (2) nonachlazine's positive chronotropic effect is substantially less marked than the inotropic one; (3) nonachlazine decreases the intensity of chronotropic reactions of the heart induced by isopreterenol. Biochemical analysis showed that in addition to its activation of oxidative phosphorylation, the ability of nonachlazine to stimulate glycogenolysis is also of importance in the development of its antianginal effect. This conclusion has been suggested by the following: (1) in acute myocardial ischemia, nonachlazine decreased lactate level and increased ATP level up to the norm; (2) at day 3 after ligation of the coronary artery, nonachlazine did not change lactate content, increased ATP and NAD, and decreased NADH2; (3) in experiments on rabbit myocardial mitochondria in vivo and in vitro nonachlazine was found to stimulate oxidative phosphorylation; (4) nonachlazine was found capable of increasing the norepinephrine level and of increasing phosphorylase a activity and the rate of glycogenolysis.

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D007773 Lactates Salts or esters of LACTIC ACID containing the general formula CH3CHOHCOOR.
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D009243 NAD A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed) Coenzyme I,DPN,Diphosphopyridine Nucleotide,Nadide,Nicotinamide-Adenine Dinucleotide,Dihydronicotinamide Adenine Dinucleotide,NADH,Adenine Dinucleotide, Dihydronicotinamide,Dinucleotide, Dihydronicotinamide Adenine,Dinucleotide, Nicotinamide-Adenine,Nicotinamide Adenine Dinucleotide,Nucleotide, Diphosphopyridine
D009628 Nonachlazine Coronary vasodilator with a novel mechanism of action; proposed as antianginal agent. Azaclorzine,Nonachlazin,Nonakhlazin
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010085 Oxidative Phosphorylation Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. Phosphorylation, Oxidative,Oxidative Phosphorylations,Phosphorylations, Oxidative
D010640 Phenothiazines Compounds containing dibenzo-1,4-thiazine. Some of them are neuroactive.
D003327 Coronary Disease An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. Coronary Heart Disease,Coronary Diseases,Coronary Heart Diseases,Disease, Coronary,Disease, Coronary Heart,Diseases, Coronary,Diseases, Coronary Heart,Heart Disease, Coronary,Heart Diseases, Coronary

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