ABSTRACT
The Department of Pharmacology of the Moscow Medical Academy has a renowned history of long standing. The course of pharmacology was read for the first time at the Medical Faculty of the Moscow University in 1764. The Department of Pharmacology was organized in 1804 and was headed during its existence by many eminent scientists (see the Table) who richly contributed to the development of Russian Pharmacology. The history of the Department of Pharmacology of the Moscow Medical Academy from the time of its foundation till 1957 has been set forth briefly by collaborators of the Department in a series of publications (V. G. Dagurov and A. A. Myazdrikova, 1981;. V. G. Dagurov, 1983, 1987; D. N. Samoilov, 1991). This article is dedicated to 70th birthday of professor D. A. Kharkevich and 40 years (1957-1997) of this activity in the department of pharmacology of the Sechenov Moscow Medical Academy. In 1957 D. A. Kharkevich was appointed as a docent, in 1963--professor and since 1964--he was been the chairman of this department.
Subject(s)
Pharmacology, Clinical/history , Schools, Medical/history , History, 20th Century , Moscow , Russia , USSRABSTRACT
The kinetics of enzymatic cholinesterase hydrolysis of dicarboxylic acid esters with neuromuscular blocking activity was studied in vitro. The maximum hydrolysis rate was shown to increase on elongation of the distance between ester groups both in the compounds containing a hydrophobic adamantyl radical attached to quaternary nitrogen and in bis-esters not containing adamantyl radicals. The comparison of neuromuscular blocking activity in vivo, enzymatic hydrolysis rates and activity on isolated skeletal muscle of some compounds demonstrated that in vivo activity is in a higher correlation with the maximum hydrolysis rate of the compounds that with activity in isolated skeletal muscle before or after cholinesterase inhibition.
Subject(s)
Dicarboxylic Acids/pharmacology , Neuromuscular Nondepolarizing Agents , Abdominal Muscles/drug effects , Abdominal Muscles/enzymology , Animals , Cholinesterases/metabolism , Dicarboxylic Acids/pharmacokinetics , Horses , Hydrolysis , In Vitro Techniques , Neostigmine/pharmacology , Ranidae , Structure-Activity RelationshipABSTRACT
The kinetics of cholinesterase enzymatic hydrolysis of carboxylic acid adamantyl derivatives was studied in vitro. The maximal rate of enzymatic hydrolysis in the series of bis-esters was shown to increase on elongation of the distance between ester groups. The maximal hydrolysis rate in the series of bis- and mono-esters decreases on elongation of the distance between ester group and quaternary nitrogen atom. The addition of adamantyl radical to the alcohol part of the molecule of bis- and mono-esters prevents the hydrolysis. The addition of lipophilic radicals to the cationic group of derivatives of mono- and dicarboxylic acids exerts a greater effect on the maximal hydrolysis rate in monoesters than in bis-esters.
Subject(s)
Carboxylic Acids/pharmacokinetics , Cholinesterases/blood , Dicarboxylic Acids/pharmacokinetics , Animals , Horses , Hydrolysis , In Vitro Techniques , Structure-Activity RelationshipABSTRACT
Tests on cats showed the compound RGH 1106 to possess an antidepolarizing mechanism of action. The sequence of myorelaxation, arising under the effect of this agent, is characterized by relaxation in the first place of the musculus masseter, muscles of limbs, then of abdominal muscles and those of the diaphragm and, finally, of the intercostal muscles. RGH 1106 doses not possess cardiotropic m-cholinolytic action, does not exert a ganglion blocking effect, nor affects the central nervous system. It neither changes the blood supply of the myocardium and the uptake of oxygen by the latter, nor inhibits the acetylcholinesterase.
