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 receiving non-depolarizing muscle relaxants during anesthesia and intensive care. However, little is known about the influence of PDE III inhibitors on the effects of non-depolarizing muscle relaxants. The aim of this study was to elucidate the effects of milrinone, a PDE III inhibitor, on d-tubocurarine (dTc)-induced muscle relaxation in vitro and then to compare its effects with those of other activators of the adenylate cyclase (AC) system (aminophylline, a non-selective PDE inhibitor; forskolin, a direct AC activator; and isoproterenol, a beta-adrenoceptor agonist). Isometric twitch tensions of rat nerve-hemidiaphragm preparations elicited by indirect or direct stimulation (0.1 Hz) were measured. Indirectly elicited twitch tension partially depressed by dTc (1 microM) was antagonized by milrinone, aminophylline, and forskolin but was attenuated by isoproterenol. Directly elicited twitch tension 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.
Narimatsu
E
E
Department of Anesthesiology, Sapporo Medical University School of Medicine, Hokkaido, Japan. enarimat@sapmed.ac.jp
Nakayama
Y
Y
Aimono
M
M
Fujimura
N
N
Iwasaki
H
H
Namiki
A
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects; D004347:Drug Interactions; D004558:Electric Stimulation; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D020105:Milrinone / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000318:Adrenergic beta-Agonists; D003473:Neuromuscular Nondepolarizing Agents; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D000628:Aminophylline; D020105:Milrinone; D007545:Isoproterenol