THE MODE OF ACTION OF NEOSTIGMINE AND PHYSOSTIGMINE ON THE GUINEA-PIG TRACHEALIS MUSCLE.

Neostigmine (2.2 mug/ml.) or physostigmine (3.3 mug/ml.) contracted guinea-pig isolated tracheal chains. The anticholinesterase diisopropylphosphodiamidic fluoride (mipafox) itself caused no contractile response even in concentrations of 100 mug/ml., yet neostigmine or physostigmine still caused contractions after treatment with mipafox. The responses were abolished by hyoscine or atropine. Local anaesthetics, cooling, ionic changes and hemicholinium, all known to inhibit the release of acetylcholine from nerve endings, abolished or much reduced the responses. It seems that the contractile response to physostigmine or neostigmine does not depend on their anticholinesterase activity, but on their ability to release acetylcholine from postganglionic parasympathetic nerve endings.