STUDIES ON SYNTHETIC CURARIZING AGENTS

¹ Merck Institute for Therapeutic Research, Rahway, N. J.

1. Sixteen compounds were tested for curariform action in mice. Most of the compounds produced marked hypotension when injected intravenously in cats and dogs but three, p-di--dimethylaminoethoxybenzene diethiodide (Diethamine), p-di-3-dimethylaminopropoxybenzene diethiodide (Dipropamine), and tris-(triethyl--ethoxyammonium)-1,2,3-benzene triiodide (Flaxedil), were relatively free of this effect, especially the latter two.

2. Dipropamine resembles d-tubocurarine in certain respects (paralysis of muscle to indirect but not to direct stimulation, and raising the threshold to intra-arterial acetyicholine), but differs in others (slowness of onset of action, irreversibility to neostigmine, failure to antagonize acetylcholine on the isolated frog muscle preparation). Therefore, Dipropamine resembles C10 in many respects.

3. Flaxedil possesses curarizing properties very closely resembling those of d-tubocurarine, and is readily reversed by neostigmine.

4. In an animal to which a dose of Dipropamine or Diethamine has been previously given, neostigmine will no longer reverse the action of Flaxedil or d-tubocurarine. This effect may be temporarily prevented if Flaxedil or d-tubocurarine is given immediately prior to Dipropamine. But even in such preparations, irreversibility to neostigmine eventually sets in, and is of long duration.

5. Neuromuscular paralysis produced by d-tubocurarine or Flaxedil may be relieved by a dose of Dipropamine which by itself would cause paralysis. The converse of this is also true. Thus, there appears to be a mutual competitive inhibition between Dipropamine and d-tubocurarine or Flaxedil. On the other hand, Flaxedil and d-tubocurarine are additive in their effects.