THE RATE OF ACTION OF ATROPINE

¹ Departments of Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York, and Harvard Medical School, Boston, Massachusetts

The rate of action of atropine has been studied in isolated guinea-pig atria, perfused hearts (Langendorff) and longitudinal muscle strips from the guinea-pig ileum. Evidence for a relatively rapid atropine-receptor reaction was obtained by direct observation of hearts perfused at high perfusion pressures, and also from the action of fast-acting antagonists in the presence of atropine in atria and ileum, and from the acceleration of the effect of atropine by pretreatment with dibenamine. In view of this evidence, it appears that the rate of action of atropine in isolated atrium and ileum (or longitudinal muscle strips) is limited by the rate of access of atropine to the receptor region, and not by the rate of the atropine-receptor reaction. The evidence in the literature appearing to support the opposite view is discussed, and it is argued that an access-limited model may be found to explain all the facts. In particular, the affinity of a drug for the muscarinic receptor will be the factor governing its rate of action. The precise roles of such factors as pacemaker shifts, special diffusion barriers and various drug-binding sites other than receptors have not yet been worked out.