Milrinone, a phosphodiesterase III inhibitor, antagonizes the neuromuscular blocking effect of a non-depolarizing muscle relaxant in vitro

Phosphodiesterase (PDE) inhibitors are occasionally used in patients receiv ing nondepolarizing muscle relaxants during anesthesia and intensive care. However, little is known about the influence of PDE III inhibitors on the e ffects of non-depolarizing muscle relaxants. The aim of this study was to e lucidate the effects of milrinone, a PDE III inhibitor, on d-tubocurarine ( dTc)-induced muscle relaxation in vitro and then to compare its effects wit h those of other activators of the adenylate cyclase (AC) system (aminophyl line, a non-selective PDE inhibitor; forskolin, a direct AC activator; and isoproterenol, a beta-adrenoceptor agonist). Isometric twitch tensions of r at nerve-hemidiaphragm preparations elicited by indirect or direct stimulat ion (0.1 Hz) were measured. Indirectly elicited twitch tension partially de pressed by dTc (1 mu M) was antagonized by milrinone, aminophylline, and fo rskolin but was attenuated by isoproterenol. Directly elicited twitch tensi on was increased by aminophylline, forskolin, and isoproterenol but was not altered by milrinone. The results indicate that milrinone antagonizes dTc- induced muscle relaxation by recovering the neuromuscular transmission. It is noteworthy that PDE inhibitors and a beta-adrenergic agonist affect non- depolarizing muscle relaxation in opposite direction.