The evidence for chemical transmission, or for neurohumoral mechanism, as the late Dr. Cannon at Harvard has called it, goes back to Claude Bernard, who observed that fatigue and block produced by curare were localized at the junctions between the nerve fibers and the excitable cell. Very soon after that, in 1877, DuBois-Reymond recognized the possibility of chemical transmission between the nerve cell and the receptor and found that this may be the result of the liberation of a chemical stimulant rather than of an electrical process. After that, it was recognized that some of the actions of the autonomic nervous system could be duplicated by drugs. Probably the first example of this was the finding that muscarine applied to the frog's heart caused a slowing of the rate very similar to that produced by stimulation of the vagus nerve. We all have become familiar with the term "muscarinic action"
BING RJ. Importance of Chemical Transmission in Cardiology and Neuropharmacology. AMA Arch Intern Med. 1959;104(4):658–671. doi:10.1001/archinte.1959.00270100144026
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