RESULTSContinuous intravenous infusion of phenylephrine, an a 1 -adrenoceptor agonist (1-6 m g/animal/min), dose-dependently decreased the Q max and voiding efficiency, and increased the P vesmax and P ves Q max , possibly by constricting urethral smooth muscle. In this functional urethral constriction model, both TAK-802 at 1 and 10 m g/kg and tamsulosin at 3 and 10 m g/kg (intravenously) caused increasing effects on the Q max and voiding efficiency. The effects were more apparent with combined exposure. Although the P vesmax was dose-dependently increased by TAK-802 alone, the effects were completely abolished by concomitant treatment with tamsulosin.
CONCLUSIONThese results suggest that TAK-802 and tamsulosin have synergistic effects in increasing the Q max and voiding efficiency, and TAK-802 does not inhibit the decreasing effect of tamsulosin on urethral resistance. That TAK-802 increased P ves when administered alone implies that monotherapy using an acetylcholinesterase inhibitor should be withheld in patients with voiding dysfunction caused by obvious bladder outlet obstruction with benign prostatic hyperplasia, to avoid disorders of the upper urinary tracts, and it should be used with an a 1 -adrenoceptor antagonist. Whether TAK-802 combined with an a 1 -adrenoceptor antagonist confers additional clinical benefit is not yet known.
KEYWORDSTAK-802, tamsulosin, acetylcholinesterase inhibitor, a 1 -adrenoceptor antagonist, urodynamics, guinea pig
OBJECTIVETo investigate the effects of TAK-802, a potent acetylcholinesterase inhibitor, and tamsulosin, an a 1 -adrenoceptor antagonist, and their concomitant administration on the urodynamic characteristics in a guinea-pig model of functional bladder outlet obstruction.
MATERIALS AND METHODSCystometry was performed in urethaneanaesthetized guinea pigs, and various urodynamic variables, including the maximum flow rate (Q max ), voiding efficiency, maximum intravesical pressure (P vesmax ) and intravesical pressure at Q max (P ves Q max ), were measured before and after administration of the drugs in combination and alone.