@article {LINEGAR191, author = {CHARLES R. LINEGAR and ROBERT P. HERWICK and THEODORE KOPPANYI}, title = {STUDIES ON THE SYNERGISM AND ANTAGONISM OF DRUGS III. FURTHER STUDIES ON THE ACTION OF NICOTINE AND PHYSOSTIGMINE ON SYMPATHETIC GANGLIA}, volume = {65}, number = {2}, pages = {191--204}, year = {1939}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Moderate doses of acetylcholine or small doses potentiated by previous administration of physostigmine produced sharp rises in blood pressure in atropinized animals. This pressor response to acetylcholine is the result of the stimulation of vasoconstrictor ganglia predominating over the peripheral vasodilator action of acetylcholine. Nicotine in appropriate amounts abolishes the rise in blood pressure from acetylcholine and converts it into a fall. It has been shown that the fall from acetylcholine after nicotine is not due to sensitization of vasodilators, for nicotine does not increase the fall from acetylcholine; it is due to incomplete atropinization. Additional atropine abolishes the fall from acetylcholine after nicotine. At the time when moderate doses of acetylcholine produce a fall in blood pressure in the nicotinized animal, large doses of acetylcholine may produce a rise. Likewise, physostigmine or prostigmin in amounts of about twice that of nicotine restored the vasopressor action of acetylcholine. The nicotine reversal of the acetylcholine pressor effect is due to two factors: (a) to depression of the ganglionic cells to acetylcholine thus interfering with the pressor effect; and (b) to the original "muscarine-like" effect of acetylcholine incompletely opposed by atropine. Physostigmine opposes the nicotine action by lowering the threshold of the ganglionic cells to acetylcholine. Atropine merely interferes with the "muscarine-like" action of acetylcholine leaving its "nicotine-like" action unaffected. In the nicotinized animal it is impossible to demonstrate the presence of sympathins liberated by the injections of acetylcholine which before the administration of nicotine raised the blood pressure and temporarily relaxed the gut.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/65/2/191}, eprint = {https://jpet.aspetjournals.org/content/65/2/191.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }