Dose-dependent effects of atropine on behavioral and physiologic responses in humans

Atropine is an antimuscarinic which has been frequently studied with learning and performance tasks using both human and animal subjects. However, interpretation of data from human studies is limited by the relatively narrow range of doses used in most such studies. In the present study a wide range of atropine doses (0, 1.5, 3.0, 6.0 mg/70 kg) were given, intramuscularly, to human volunteers to assess the effects of atropine on a variety of behavioral measures, subject ratings, and physiologic function. The time course of responses was examined over 24 hours. Behavioral measures were a computerized Performance Assessment Battery (PAB) which contained measures of logical reasoning, short-term memory and rapid arithmetic, a Digit Symbol Substitution Test (DSST), and a psychomotor test of hand-eye coordination (Circular Lights). Administration of atropine produced both time- and dose-dependent effects on most measures used, although sensitivity varied across measures. At the 1.5 mg dose, no effects on performance were detected, however, after 6.0 mg reliably and 3.0 mg occasionally, impairments occurred on measures of accuracy and speed of performance. These effects generally began by 1.5 hours postdrug and returned to baseline by 7-9 hours postdrug. In contrast, certain subject ratings and physiologic variables were affected by lower doses of atropine, showing deviations from baseline at 1.5 mg and producing a time course of effects that was both earlier in onset and longer in duration than was observed with the performance measures. The present results have practical implications for the clinical utilization of atropine in situations in which optimal performance is required.