Shakuyakukanzoto (SKT) is a kampo medicine\ncomposed of equal proportions of Glycyrrhizae radix\n(G. radix) and Paeoniae radix (P. radix). A double-blind\nstudy reported that SKT significantly ameliorated painful\nmuscle cramp in cirrhosis patients without the typical\nsevere side effects of muscle weakness and central nervous\nsystem (CNS) depression. Previous basic studies reported\nthat SKT and its active components induced relaxation by a\ndirect action on skeletal muscle and that SKT did not depress\nCNS functions; however, why SKT has a lower incidence\nof muscle weakness remains unknown. In the\npresent study, we investigated which components are absorbed\ninto the blood of rats after a single oral administration\nof SKT to identify the active components of SKT.\nWe also investigated the effects of SKT and its components\non the twitch contraction induced by physiological Ca2?\nrelease. Our study demonstrated that SKT and five G. radix\nisolates, which are responsible for the antispasmodic effect\nof SKT, did not inhibit the twitch contraction in contrast to\ndantrolene sodium, a direct-acting peripheral muscle relaxant,\nindicating that the mechanisms of muscle contraction\nof SKT and dantrolene in skeletal muscle differ. These\nfindings suggest that SKT does not reduce the contractile\nforce in skeletal muscle under physiological conditions, i.e., SKT may have a low risk of causing muscle weakness\nin clinical use. Considering that most muscle relaxants and\nanticonvulsants cause various harmful side effects such as\nweakness and CNS depression, SKT appears to have a\nbenign safety profile.
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