Clonidine increases the sweating threshold, but does not reduce the gain of sweating

We tested the hypothesis that clonidine produces a dose-dependent increase in the sweating threshold but does not reduce the gain of sweating. Six healthy male volunteers were evaluated, each on three separate days in random order. In one, saline was administered; in another, a 2-micrograms/kg bolus of clonidine was followed by an infusion at 2 micrograms.kg-1.h-1, and on a third day, a 4-micrograms/kg bolus was followed by an infusion at 4 micrograms.kg-1.h-1. Core temperature was measured at the tympanic membrane and mean skin temperature was determined from four sites. A chest sweating rate of 40 g.m-2.h-1 was considered significant. The core temperature triggering sweating, adjusted to a designated mean skin temperature of 34 degrees C, identified the threshold for this response. Gain was defined by the adjusted core temperature increase required to augment sweating from 100 to 300 g.m-2.h-1. degree C-1. Plasma clonidine concentrations were 0.8 +/- 0.1 and 1.6 +/- 0.2 ng/mL on the small- and large-dose days, respectively. Clonidine administration increased the sweating threshold approximately 0.4 degree C (P < 0.05), but the increase was comparable at each dose. The gain of sweating was approximately 0.2 degree C and was not influenced by clonidine administration. The thermoregulatory effects of clonidine thus resemble those of volatile anesthetics, opioids, and propofol. These data suggest that the antishivering effect of clonidine results from central thermoregulatory inhibition rather than a specific peripheral action on thermogenic muscular activity. Unlike other sedatives and anesthetics, the concentration-dependence of clonidine demonstrates a ceiling beyond which the administration of an additional drug fails to enhance the effect, suggesting that the thermoregulatory effect of clonidine may be limited, even at high plasma concentrations. The gain of sweating was well preserved indicating that this response remains effective in the presence of sedatives and anesthetics.