SPECTRUM OF ACTION OF MUSCARONE AND DERIVATIVES

¹ Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois

The spectrum of action of (-) muscarone, its isomers (+) and dl-muscarone and dl-allo-muscarone, and of two derivatives of musearone was compared to that of L-(+) muscarine and of acetylchohine. Quantitative studies regarding their action at postganglionic parasympathetic effector sites and at Peripheral ganglionic and neuromuscular synapses were made in a variety of test preparations in different species.

Muscarones, and in particular (-) muscarone, were significantly more potent than L-(+) muscarine and acetylcholine in stimulating post-ganglionic parasympathetic sites. Introduction of a double bond into the tetrahydrofurane ring of dl-muscarone or substitution of the 2-methyl group of muscarone by n-propyl decreased muscarinic potency.

In contrast to muscarine, muscarone and its isomers and derivatives possessed appreciable ganuglionic stimulant properties as evidenced by their stimulatory effects on the nictitating membrane of atropinized cats dogs and on the dog pelvic nerve bladder preparation after atropinization. In those tests, the muscarones were as active as acetylcholine. Their ganglionic stimulant potency was not correlated with their muscarinic potency. On the isolated frog rectus abdominis muscle most of the muscarones surpassed acetylcholine in potency.

Lethal effects of the muscarones were not correlated with their muscarinic potencies; the lethal effects were nt antoagonized by cholinergic blocking agents (atropine, atropine methyl bromide, pentolinium).