thymodepressin and 6-methyluracil

The effect of C-547, a tetraalkylammonium derivative of 6-methyluracil, a novel highly selective acetylcholinesterase inhibitor, on frog neuromuscular junction was studied. In concentrations 10(-9)-10(-7)M the preparation increased the amplitude and temporal parameters of miniature endplate potentials. In contrast to the effect of C-574 on purified acetylcholinesterase from mammals, the effect of this agent on frog neuromuscular junction was reversible. In a concentration of 10(-6)M the preparation apart from anticholinesterase activity produced a parasympatholytic effect manifested in a decrease in amplitude and decay time constant of miniature endplate potentials accompanied by a decrease in spontaneous transmitter secretion. After washout, the parasympatholytic effect recovered more slowly, but disappeared more rapidly compared to anticholinesterase activity. These findings suggest that parasympatholytic effect of C-547 results from direct action on receptor-channel complexes in the endplate membrane.

Topics: Acetylcholinesterase; Animals; Dose-Response Relationship, Drug; Electrophysiology; Enzyme Inhibitors; Membrane Potentials; Neuromuscular Junction; Peptides; Quaternary Ammonium Compounds; Ranidae; Time Factors; Uracil