3,6-BIS(3-DIETHYLAMINOPROPOXY) PYRIDAZINE BISMETHIODIDE, A LONG-ACTING NEUROMUSCULAR BLOCKING AGENT

¹ Pharmacology Section , Sterling-Winthrop Research Institute, Rensscler, New York

Studies on the mechanism of actions of Compoumsd V have revealed: 1) neuromuscular blockade following Compound V in the cat sciatic-gastrocnemius preparation is primarily dependent upon the fuequency of nerve stimulation and the blockade is neither the result of contraction fatigue nor the result of altered nerve conduction; 2) Compound V does not antagonize acetylcholine on the frog rectus abdominis preparations, but 3) it produces a flaccid paralysis in the pigeon; 4) its neuromuscular blocking effects are partially antagonized by neostigmine; 5) it reduces the response of the denervated and normal gactrocnemius of the cat to intraarterial acetyleholine, and 6) a short tetanus of the gastrocnemius of the cat blocked with Compound V is not sustained and is followed by a posttetanic potentiation; yet 7) it has weak excitatory effects on the frog rectus abdominis and the denervated cat gastroenemius, as well as an anticurare action in the cat nerve-muscle preparation.

It is concluded that Compound V has a mode of action different from that of either d-tubocurarine or decamethonium, although its site of action appears to be at the postjunctional membrane. As a working hypothesis a mechanism is suggested which provides an explanation for many of the unusual effects of Compound V at the myoneural junction.