PARASYMPATHOMIMETIC EFFECTS OF THE ETHYLAL OF -TRIMETHYLAMMONIUMPROPANEDIOL IODIDE (F2268)

¹ Department of Pharmacology, Harvard Medical School, Boston, Mass.

1. The ethylal of -trimethylammoniumpropanediol iodide (F2268) has a pressor action in atropinized intact and spinal cats. A dose of 1 to 10 mgm./kgm. of F2268 is usually required to produce this action, which is due to ganglionic stimulation.

2. When a dose of 6 mgm./kgm. of F2268 is given repeatedly to atropinized spinal cats, two effects are seen. Initially a stepwise increase in the pressor response to successive doses occurs. Later an interfering action, which probably represents ganglionic block, becomes evident.

3. When a dose of 6 mgm./kgm. of F2268 is given repeatedly to atropinized spinal cats, a depressor action can be observed after the pressor action has been abolished by tetraethylammonium. The depressor action remains constant with repeated doses.

4. When repeated doses of 1 mgm./kgm. of acetylcholine bromide and 6 mgm./kgm. of F2268 are given alternately to atropinized spinal cats the pressor response to acetylcholine shows an initial stepwise increase and a later decrease, while the pressor response to F2268 shows only a steady decrease.

5. In unatropinized animals, F2268 exerts typical muscarinic actions on heart rate, blood pressure, secretion of salivary, lacrimal and bronchial glands, and intestinal smooth muscle. In doses of 10 microgm. or more, F2268 is more potent than methacholine chloride in lowering the blood pressure, slowing the heart rate, and causing cardiac arrhythmias. F2268 exerts a more prolonged muscarinic action on the heart than does methacholine.