RT Journal Article
SR Electronic
T1 THE ACTION OF AMBENONIUM (WIN 8077) AND RELATED COMPOUNDS IN THE MOUSE
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 541
OP 549
VO 119
IS 4
A1 A. M. Lands
A1 J. O. Hoppe
A1 A. G. Karczmar
A1 Aaron Arnold
YR 1957
UL http://jpet.aspetjournals.org/content/119/4/541.abstract
AB The results presented above provide some new data on various pharmacologic actions on mouse voluntary muscle of several benzoquinoniums, ambenonium and ambenonium-like compounds in comparison with the actions of neostigmine, edrophonium and various other well known drugs. Ambenonium, benzoquinonium and related compounds have little direct stimulating action (Hoppe, 1951; Karczmar, 1957) but do sensitize to the stimulating (and paralyzing) actions of ACh and neostigmine. This action is greatly reduced or changed to d-tubocurarine-like blockade by relatively simple changes in structure such as replacement of a benzyl group in the ammonium center by an ethyl group (benzoquinonium vs. Win 7846) or by changes in the ring substitutions of the benzyl group (ambenonium vs. Win 8076). The potentiating action observed appears with compounds that are effective inhibitors of AChE. However, there is no overall correlation among these compounds as to AChE inhibitory potency and effectiveness in potentiating the actions of ACh and neostigmine. Furthermore, antidotal activity against tetraethylpyrophosphate toxicity in mice bears no direct relationship to effectiveness in inhibiting AChE. The above data, and that of other investigators of nerve-muscle transmission, lead us to suggest that transmission at the neuromyal junction may be modified by 1) direct action of applied substances, 2) the accumulation of endogenous ACh following AChE inhibition and 3) the introduction of substances which modify some essential step in the transmission process, other than that involving AChE.