Evaluation of the cardiovascular effects of arecoline in the anesthetized dog

Abstract

Beil, M.E., F.R. Goodman, H.H. Shlevin, and E.F. Smith 111: Evaluation of the cardiovascular effects of arecoline in the anesthetized dog. Drug Dev. Res. 9:203-212, 1986. 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 mglkg methyl scopolamine (group 111). In group I, mean arterial blood pressure (MABP) was immediately reduced (i.e., within 1 min) after each dose of arecoline, but had returned to the baseline value by 5 min after doses of 0.01 to 10 pglkg, and by 20 min after a 30 pgl kg dose. However, blood pressure was still depressed 20 min after a 100 pglkg dose of arecoline. Cardiac output (CO) was significantly reduced only after the 30 or 100 pglkg doses. In group II, MABP, heart rate (HR), and CO were unchanged after a 0.3 or 1.0 pgl kglmin infusion of arecoline. An infusion of 3.0 or 10 pglkglmin produced dose-dependent decreases in MABP ( -15 and -56%, respectively) and HR ( -13 and -71%, respectively). CO was unchanged at 3 pglkglmin but was reduced by 50% at 10 pglkglmin (P < 0.05). Plasma levels of arecoline were 46.9 f 5.5 nglml after an arecoline infusion of 10 pglkglmin. Pretreatment with methyl scopolamine significantly attenuated the cardiodepression produced by 10 pglkglmin arecoline. Moreover, infusions of 30 and 100 pglkgl 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 ngl ml with an infusion of 10 or 100 pglkglmin, respectively. These data indicate that the continuous administration of a low dose of arecoline may minimize the undesired cardio-

Cognition activators

“…292 The action of arecoline on levels of acetylcholine, norepinephrine, and dopamine in the mouse central nervous system (CNS) has been reviewed, 293 and cardiovascular effects of arecoline in the anesthetized dog have been studied. 294 Combinations of agonists (e.g., arecoline plus oxotremorine) do not clearly display supra-additive enhancement of memory in a mouse T-maze active avoidance paradigm, despite reports to the contrary. 295 Pilocarpine is a muscarinic receptor agonist widely used as a topical miotic for controlling elevated intraocular pressure associated with glaucoma, but the drug has sipficant delivery problems.296 Analogues of pilocarpine have not been well explored in cognition despite facile synthetic routes to this series.297 The synthesis, physicochemical properties, and kinetics of lactonization of pilocarpic acid esters have been reported,298 and the binding of isopilocarpine to muscarinic cholinergic receptors has also been studied.…”