ABSTRACT
A few derivatives of natural, bicyclic monoterpenes, which are propranolol analogs, were synthetized. Those compounds were studied pharmacologically in order to determine their toxicity, antiarrhythmic activity in selected experimental models of arrhythmia, the local anesthetic effect and influence on the cardiovascular system. The tested compounds showed a less potent or similar toxicity towards reference drugs, were devoid of an antiarrhythmic activity in the model of barium arrhythmia, yet some of them (compounds 9 and 12) increased the arrhythmogenic dose of strophanthin. All the compounds studied had a local anesthetic effect stronger than lidocaine in infiltration anesthesia, and compound 8--also in surface anesthesia.
Subject(s)
Arrhythmias, Cardiac/prevention & control , Blood Pressure/drug effects , Heart/drug effects , Propranolol/analogs & derivatives , Anesthetics, Local , Animals , Chromatography, Gas , Chromatography, Thin Layer , Female , Guinea Pigs , Male , Mice , Propranolol/chemical synthesis , Propranolol/chemistry , Propranolol/pharmacology , Rats , Rats, Wistar , Structure-Activity Relationship , Terpenes/analysisABSTRACT
Esters of N,N-diethylaminoacetic acid and hydroxyamines, obtained from structurally different natural monoterpenes, were pharmacologically examined. It was proved that salts of the obtained compounds had local anesthetic properties in infiltration anesthesia, compounds 9, 6 and 8 having been more potent than lidocaine. Compounds 7-9 slightly increased the arrhythmogenic dose, and compound 12 - the lethal dose of strophanthin. All the examined compounds transiently decreased the arterial blood pressure and displayed a cardiopressive activity.
Subject(s)
Anesthetics, Local/chemical synthesis , Cardiovascular Agents/chemical synthesis , Hydroxylamines/chemical synthesis , Terpenes/chemical synthesis , Anesthetics, Local/pharmacology , Anesthetics, Local/toxicity , Animals , Anti-Arrhythmia Agents/chemical synthesis , Anti-Arrhythmia Agents/pharmacology , Anti-Arrhythmia Agents/toxicity , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/prevention & control , Blood Pressure/drug effects , Cardiovascular Agents/pharmacology , Cardiovascular Agents/toxicity , Chromatography, Gas , Chromatography, Thin Layer , Guinea Pigs , Heart/drug effects , Hydroxylamines/pharmacology , Hydroxylamines/toxicity , In Vitro Techniques , Lethal Dose 50 , Male , Mice , Rats , Rats, Wistar , Terpenes/pharmacology , Terpenes/toxicityABSTRACT
Synthesis and physicochemical and pharmacological properties of 10 analogs of 2-[2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)ethoxy]N, N-diethylamino ethane (3) have been described. The compounds possess toxicity close to or lower than the parent compound--myrtecaine, have no antiarrhythmic activity but some of them (15, 16, 22, 24), similarly as compound 3, show quite strong local anesthetic action.
