Central and peripheral anticholinergic potency of some drugs antagonistic to anticholinesterase poisoning

Abstract

MADILL, H. U., STLWART, V(i. C., AND SAVOYE, M. L. 4948. Central and peripheral antichoIinergic potency of some drugs antagonistic to anticholinesterase poisoning. Can. J. Physiol. Pharmcol. 46, 559-565.The central and peripheral anticholinergic potency of nine drugs together with their therapeutic effectiveness in treating satin poisoning was measured and compared with atropine. There was a direct relationship between the anticholinergic poteilcies of these drugs as measured by tests indicative of activity in the central nervous system and their therapeutic effectiveness in treating sarin poisoning. One exception to this was shown by the drug cararniphen, which s h o~e d significantly higher therapeutic protection than the drug atropine at equinlolar dosages, yet was less active as a peripheral or central anticholinergic drug. High levels of therapeutic protection were directly rclatcd to high levels of central anticholinergic potency.

Dual mechanism of the antidotal action of atropine-like drugs in poisoning by organophosphorus anticholinesterases

“…Atropine has long been used in the treatment (Wills, 1964) of poisoning by anticholinesterases on the simple basis that it blocks the effects of excess of acetylcholine a t muscarinic receptors in the central nervous system (cns) and in the periphery (pns). The potential usage of synthetic organophosphorus compounds as chemical warfare agents (Heath, 1961) and the increasing use of organophosphorus compounds as insecticides (Eto,I974), make poisoning by anticholinesterases a serious problem (Namba, 1971) and many attempts have been made (Coleman, Little & Bannard, 1962, 1963Wills, 1964;Madill, Stewart & Savoie, 1967;Brimblecombe, Green & others, 1970) to improve therapeutic procedures, most of which involve atropine-oxime mixtures, by replacing atropine by other antimuscarinic drugs. In these investigations no clear relation was demonstrated between the protection afforded by atropine-like drugs against poisoning by organophosphorus anticholinesterases and their antimuscarinic activity in the pns and cns.…”