Different sensitivity of miniature endplate currents of the rat extensor digitorum longus, soleus and diaphragm muscles to a novel acetylcholinesterase inhibitor C-547.
A novel derivative of 6-methyluracil, C-547, increased the amplitude and prolonged the duration of miniature endplate currents (MEPCs) which is typical for acetylcholinesterase inhibition. In the soleus and extensor digitorum longus significant potentiation was detected at nanomolar concentrations. In contrast, in the diaphragm muscle, the increase in the amplitudes of the MEPCs and the decay time constant appeared only when the concentration of C-547 was elevated to 1 x 10(-7) M. Possible consequences for the exploitation of this drug, which can selectively inhibit AChE in particular synapses, are discussed.
Petrov
K A
KA
Kazan Institute of Organic and Physical Chemistry, Russian Academy of Sciences, Kazan, Russia.
Kovyazina
L V
LV
Zobov
V V
VV
Bukharaeva
E A
EA
Nikolsky
E E
EE
Vyskocil
F
F
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D009045:Motor Endplate / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
C449662:C-547 compound; D002800:Cholinesterase Inhibitors; D000644:Quaternary Ammonium Compounds; D014498:Uracil