RT Journal Article
SR Electronic
T1 Comparison of central nervous system and peripheral pharmacodynamics to atropine pharmacokinetics.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1133
OP 1139
VO 255
IS 3
A1 E H Ellinwood, Jr
A1 A M Nikaido
A1 S K Gupta
A1 D G Heatherly
A1 J K Nishita
YR 1990
UL http://jpet.aspetjournals.org/content/255/3/1133.abstract
AB Two experiments were designed to examine the pharmacokinetic-pharmacodynamic relationship for the central nervous system and peripheral effects of atropine. According to a random Latin square design, healthy young male volunteers were given i.m. injections containing single doses of placebo or 0.5, 1.0, 2.0 or 4.0 mg of atropine. The central nervous system tests included wheel tracking, a coordination task, and digit symbol substitution, a memory-psychomotor speed task; the physiological variable was heart rate. The pharmacokinetics of atropine were best described by a two-compartment model with very rapid first order absorption. Changes in plasma atropine levels and heart rate closely overlapped for all four doses throughout most of the time course. In contrast, the differential time course of changes in atropine levels and behavioral impairment indicates that pharmacokinetics is not the primary rate-limiting mechanism for the central nervous system effects of atropine. Alternative explanations are discussed, including differential atropine effects on peripheral M2 receptors mediating a heart rate effect and on CNS M1 receptors mediating the memory-psychomotor effect.