Telemetric Monitoring of Physiological Signs in Conscious Beagles: Pharmacological Evaluation of a B3 Agonist, BRL 37344
Beta-3 receptors, the most recently discovered class of adrenoceptors, have been identified in a number of species including dogs where they are involved in lipolysis, vasorelaxation in the gastrointestinal tract, and vasodilation. Because stimulation of beta-3 receptors induces lipolysis, they are the targets of many emerging antiobesity drugs. A balanced crossover study, in which 8 beagles with full-implant telemetry systems were given an 8.3 mg/kg dose of the beta-3 agonist BRL 37344, was carried out to determine if BRL 37344 had substantial cardiovascular side effects which might limit its use as an antiobesity drug for dogs. The dogs' blood pressure, heart rate, and core body temperature were recorded for 24 hours after injection of the drug. Measurements revealed that this dose of BRL 37344 caused a significant decrease in systolic blood pressure from control values for 3 hours after injection and significant reflex tachycardia for 7 hours after injection. A drop in core body and rectal temperatures from control was also observed for 3.5 hours after injection. Further studies using an infrared thermometer to measure skin temperature indicated that the drops in core body temperature were caused by increased heat loss through the skin due to the vasodilatory effects of the drug. Results from these studies indicated that beta-3 agonists, specifically BRL 37344, would not be practical for use as antiobesity drugs in dogs due to their significant cardiovascular side effects.