Evaluation of the cardiovascular effects of arecoline in the anesthetized dog

Arecoline has been reported to improve memory deficits, but a relatively short half-life and adverse cardiovascular effects have limited its use. The purpose of this study was to compare the cardiovascular effects of a bolus administration with those of an infusion of arecoline in anesthetized beagle dogs. Arecoline was administered either as a 15 sec bolus (group I), as a constant infusion (group II), or as an infusion after pretreatment with 0.1 mg/kg methyl scopolamine (group III). In group I, mean arterial blood pressure (MABP) was immediately reduced (i.e., which 1 min) after each dose of arecoline, but had returned to the baseline value by 5 min after doses of 0.01 to 10 μg/kg, and by 20 min after a 30 μg/kg dose. However, blood pressure was still depressed 20 min after a 100 μg/kg dose of arecolin. Cardiac output (CO) was significantly reduced only after the 30 or 100 μg/kg doses. In group II, MABP, heart rate (HR), and CO were unchanged after a 0.3 or 1.0 μg/kg/min infusion of arecoline. An infusion of 3.0 or 10 μg/kg/min produced dose-dependent decreases in MABP (–15 and –56%, respectively) and HR (–13 and –71%, respectively). CO was unchanged at 3 μg/kg/min but was reduced by 50% at 10 μg/kg/min (P < 0.05). Plasma levels of arecoline were 46.9 ± 5.5 ng/ml after an arecoline infusion of 10 μg/kg/min. Pretreatment with methyl scopolamine significantly attenuated the cardiodepression produced by 10 μg/kg/min arecoline. Moveover, infusions of 30 and 100 μg/kg/min of arecoline produced less than 40% reductions in MABP, HR, and CO. After pretreatment with methyl scopolamine, plasma arecoline levels were 29 ± 4 and 259 ± 38.7 ng/ml with an infusion of 10 or 100 μg/kg/min, respectively. These data indicate that the continuous administration of a low dose of arecoline may minimize the undesired cardiovascular effects. Pretreatment with methyl scopolamine further attenuated the cardiovascular responses produced by arecoline, suggesting that a greater therapeutic ratio may be achieved in the presence of a peripheral muscarinic blocking agent.