Comparison of the effects of atropine in vivo and ex vivo (radioreceptor assay) after oral and intramuscular administration to man

Abstract

The effects of an oral dose of atropine (0.03 mg/kg body weight) and an IM (0.02 mg/kg) dose on the heart rate and salivary flow in seven healthy adult volunteers were compared to see whether the oral dose was sufficient to inhibit vagal reflexes of the heart. Atropine concentrations in plasma were determined by an M₂-selective radioreceptor assay, and the in vitro occupancy of porcine cardiac M₂-cholinoceptors was measured in parallel.

In ligand-binding studies, atropine has been shown to have a comparable affinity for human and porcine cardiac M₂-cholinoceptors (K_i 4.0 and 5.9, respectively). Slight changes in heart rate after oral administration were not significant. After IM administration, however, the heart rate increased significantly, by a maximum of 22 beats·min⁻¹ after 45 min. The slight increase in heart rate after the oral dose corresponded to a receptor occupancy in vitro near the lower limit of detection, whereas the significant increase in heart rate after the IM dose corresponded to a receptor occupancy of up to 47%. The maximum reduction in salivary flow was similar after the oral and IM doses (84.3 and 87.5%, respectively).

The almost complete inhibition of salivary flow could be explained by the lower vagal tone in the salivary glands compared with to the heart. The difference in the effect on heart rate was probably due to lower absorption of the oral dose. Thus, an oral dose greater than 0.03 mg atropine/kilogram body weight is required to compensate for low gastrointestinal absorption and to overcome the high vagal tone of the heart.