%0 Journal Article %A W. Schaumann %A C. Job %T DIFFERENTIAL EFFECTS OF A QUATERNARY CHOLINESTERASE INHIBITOR, PHOSPHOLINE, AND ITS TERTIARY ANALOGUE, COMPOUND 217-AO, ON CENTRAL CONTROL OF RESPIRATION AND ON NEUROMUSCULAR TRANSMISSION. THE ANTAGONISM BY 217-AO OF THE RESPIRATORY ARREST CAUSED BY MORPHINE %D 1958 %J Journal of Pharmacology and Experimental Therapeutics %P 114-120 %V 123 %N 2 %X In experiments on rats, the action potentials in the left cut phrenic nerve and the contractions of the innervated right half of the diaphragm were recorded. With this method we investigated the effects of Phospholine and compound 217-AO, two anticholinesterases of similar chemical structure, on the central control of respiration and on the neuromuscular junction. Low doses of Phospholine, which do not penetrate into the central nervous system, inhibited the neuromuscular transmission, whereas even large amounts had no central effect on respiration. Because of its better lipoid solubility, 217-AO easily penetrates the blood-brain barrier. It inhibited respiration by a direct central action without visibly impairing neuromuscular transmission. However, neuromuscular block was observed when the central effects were prevented by atropine. It was found that when the activity of the motor nerve was weak, the cholinesterase inhibitors enhanced neuromuscular transmission; but when nervous activity was strong, they blocked it. Although 217-AO inhibited the respiratory center, it antagonized the respiratory arrest produced by morphine. %U https://jpet.aspetjournals.org/content/jpet/123/2/114.full.pdf