Comparing the cardiac vagolytic effects of atropine and methylatropine in rhesus macaques.

Atropine and methylatropine (190 nmol/kg) were compared in rhesus monkeys (Macaca mulatta) for their ability to produce a cardiac vagal blockade using a noninvasive estimate of respiratory sinus arrhythmia (RSA). Twelve monkeys received both drugs via intravenous (IV) and intramuscular (IM) routes of administration and were monitored for 3 hr after treatment. Both drugs, regardless of the route of administration, reduced RSA amplitude. At this dose, methylatropine was more effective than atropine in its ability to reduce RSA amplitude, heart period (HP; beat-to-beat interval), and overall heart period variability (HPV). Estimated RSA amplitude and HPV returned to basal levels significantly earlier after IM atropine administration than after IV treatment. Methylatropine did not exhibit any route effects. In addition, the mean decrease in RSA amplitude and HPV for the IM route of atropine sulfate was significantly less than that for the IV route. Serum atropine concentrations correlated significantly with all variables after IM treatment but only with RSA and HPV after IV treatment. Methylatropine may therefore be more useful than atropine as a pharmacologic challenge drug for detecting organophosphorus (OP) exposure because of its longer duration of action, lack of route of administration differences, and less likelihood of crossing the blood-brain barrier. Further studies are needed to fully evaluate methylatropine's potential in the challenge method of OP detection.