[The study of effects of a novel acetylcholinesterase inhibitor on electrical activity of the heart].
We have investigated effect of a representative of the novel class of selective acetylcholinesterase inhibitors A 1,3-bis[5(diethyl-o-nitrobenzyl ammonio) penthyl]-6-methyluracildibromide (compound 547) on duration and rhythm of sequence of right atrial action potential (AP) as well as on kinetics of acetylcholinesterase catalyzed reaction in homogenates of skeletal muscle (m. extensor digitorum longus) and cardiac muscle in the rat. We have shown that contrary to classical acetylcholinesterase inhibitors armin and proserin none of studied concentrations (1, 10 and 100 nM) of compound 547 exerted significant effect on AP configuration and rate of sinus rhythm. Compound 547 belongs to noncompetitive type with K1(heart)=3.6 x 10(-4) M and K1(EDL)=1.3 x 10(-8) M. Proserin exerts comparable inhibitory action on reaction in the heart and skeletal muscle, its K1(heart)=0.73 x 10(-5) M and K1(EDL) = 0.4 x 10(-5) M. Thus low sensitivity of myocardium to compound 547 in electrophysiological experiments is not related to lesser availability of synaptic acetylcholinesterase in the heart compared with acetylcholinesterase in skeletal muscles but reaction catalyzed by cardiac acetylcholinesterase is actually to a substantial degree less prone to inhibition by compound 547.
Abramochkin
D V
DV
Petrov
K A
KA
Zobov
V V
VV
Iagodina
L O
LO
Nikol'skiĭ
E E
EE
Rozenshtraukh
L V
LV
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004338:Drug Combinations; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009388:Neostigmine / Q000494:pharmacology; D051381:Rats
D002800:Cholinesterase Inhibitors; D004338:Drug Combinations; D009388:Neostigmine