COMPARISON OF THE EFFECTS OF ATROPINE IN-VIVO AND EX-VIVO (RADIORECEPTOR ASSAY) AFTER ORAL AND INTRAMUSCULAR ADMINISTRATION TO MAN

The effects of an oral dose of atropine (0.03 mg/kg body weight) and a n IM (0.02 mg/kg) dose on the heart rate and salivary flow in seven he althy adult volunteers were compared to see whether the oral dose was sufficient to inhibit vagal reflexes of the heart. Atropine concentrat ions in plasma were determined by an M(2)-selective radioreceptor assa y, and the in vitro occupancy of porcine cardiac M(2)-cholinoceptors w as measured in parallel. In ligand-binding studies, atropine has been shown to have a comparable affinity for human and porcine cardiac M(2) -cholinoceptors (K-i 4.0 and 5.9, respectively). Slight changes in hea rt rate after oral administration were not significant. After IM admin istration, however, the heart rate increased significantly, by a maxim um of 22 beats . min(-1) after 45 min. The slight increase in heart ra te after the oral dose corresponded to a receptor occupancy in vitro n ear the lower limit of detection, whereas the significant increase in heart rate after the IM dose corresponded to a receptor occupancy of u p 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 how 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 o ral dose. Thus, an oral dose greater than 0.03 mg atropine/kilogram bo dy weight is required to compensate for lo ur gastrointestinal absorpt ion and to overcome the high vagal tone of the heart.