The central and peripheral activities of anti-acetylcholine drugs. Some concepts of practical relevance

Abstract

Abstract Five procedures have been used to compare the pharmacological effects and time-activity profiles of anti-acetylcholine drugs in the central and peripheral nervous system (ens, pns). In particular, the potencies of optically pure enantiomers of anti-acetylcholine drugs which contain an asymmetric centre have been determined. The following four observations are made which are of relevance to all studies of anti-acetylcholine drugs. (1) Times to onset of activity of anti-acetylcholine drugs in three in vivo tests and the duration of action in one in vivo test are shown to increase as affinity constants, determined in vitro, increase. (2) Below a dose of ca 0.03 μmol kg−1no anti-acetylcholine drug produces maximum mydriatic effects and all anti-acetylcholine drugs which have log affinity constant values >9.49 produce maximal effects at approximately this dose. (3) The receptor with which anti-acetylcholine drugs interact is essentially the same in the eye, salivary gland and ens of the mouse, the guinea-pig ileum, and in the cat ens. (4) For any anti-acetylcholine drug the time to onset of effects in the ens is similar to the time of onset of effects in the pns and appears to depend on the affinity constant rather than on the partition properties of the drug. The practical and theoretical significance of these and other observations are discussed.