Effects of several aminopyridines and analogs on the calcium dependence of synaptic transmission.

The effects of 4-aminopyridine (4-AP), 4-AP methiodide (4-APMI), 3,4-diaminopyridine (3,4-DAP), 4,5-diaminopyrimidine (4,5-DAPM) and 4-dimethylaminopyridine (4-DMAP) on synaptic transmission in isolated frog sympathetic ganglia were examined by means of extracellular recording. Ganglia were exposed to graded reductions in extracellular Ca++, from the normal 1.8 mM in the absence and in the presence of drugs while recording amplitudes of the transmitted postganglionic compound action potential. The amplitudes of compound action potential relative to those in normal Ca++ were then plotted as a function of log Ca++ concentration. In the absence of drugs, transmission failed progressively as Ca++ was reduced from 1.8 to 0.47 mM. However, the curve of the compound action potential amplitude vs. log Ca++ was shifted to the left (lower Ca++) by all drugs in a dose-dependent fashion. The drugs varied in effectiveness in shifting the Ca++ dependence curve to the left, the order being: 3,4-DAP greater than or equal to 4-AP greater than or equal to 4,5-DAPM greater than 4-APMI greater than 4-DMAP. 4-AP, 3,4-DAP and 4,5-DAPM were also able to generate repetitive postganglionic discharge in response to a single orthodromic stimulus. All drugs, except 4,5-DAPM, were able to block synaptic transmission at higher concentrations, and their blocking potencies were in the following order: 4-DMAP greater than or equal to 4-APMI greater than or equal to 3,4-DAP greater than or equal to 4-AP.(ABSTRACT TRUNCATED AT 250 WORDS)