Intramuscular and intravenous atropine: comparison of effects in the heat-stressed rat

In our rat model of human heat injury we have administered atropine intravenously (iv); for clinical use in man, administration is by either the intramuscular (im) or iv route. In order to determine potential differences due to route of administration, we compared the dose-response effects of im and iv administration in rats. Adult male rats (500 g) were heat-stressed (41.5 degrees C) while unrestrained which enabled them to thermoregulate by saliva spreading activity. We quantitated the effects of im or iv atropine (10-4000 micrograms.kg-1) on the following variables: heating rate (rate of rise of core temperature), % weight loss (saliva production), and fecal loss (intestinal motility). Further, we examined the effects of atropine on pupil dilation in restrained rats at 26 degrees C. Heating rate was identical for both routes of atropine administration at 200 micrograms.kg-1 (equivalent to the standard 2-mg dosage in man), but the range of doses over which there was a dose-response effect on heating rate with iv administration (10-1000 micrograms.kg-1) was markedly truncated with the im route (10-50 micrograms.kg-1). Both im and iv atropine had similar effects on weight loss rate and mydriasis. The iv route is preferred because that route produced the most consistent results and the most sensitive physiological response (heating rate) is affected over a wider dose range.