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- W2107266355 abstract "The present study was designed to further evaluate a possible spasmolytic activity of synthetic lapachol derivatives, norlapachol, α-norlapachone, β-norlapachone and hydro-hydroxy- norlapachol (HH-norlapachol), on guinea-pig ileum. In guinea-pig ileum, except for norlapachol, all naphthoquinones inhibited the phasic contractions induced by carbachol or histamine. Even when the ileum was pre-contracted with KCl, carbachol or histamine, all naphthoquinones induced relaxation, suggesting that these naphthoquinones could be acting on the voltage-gated calcium channels (Ca V ). As the tonic component this contraction is maintained mainly by the opening of the Ca V , we hypothesized that these naphthoquinones might be acting on these channels. This hypothesis was confirmed by the observation that norlapachol (pD’2 = 4.99), α-norlapachone (pD’2 = 4.49), β-norlapachone (pD’ 2 = 6.33), and HH-norlapachol (pD’ 2 = 4.53) antagonized the contractions induced by CaCl 2 in depolarizing medium nominally without Ca 2+ . As β-norlapachone was the most potent we decided to continue the study of its action mechanism. The fact that this naphthoquinone has inhibited the tonic contractions induced by S-(-)-Bay K8644 [EC 50 = (1.6 ± 0.30) · 10 -5 M] suggests that the Ca 2+ channel involved belongs to the type L (Ca V 1.2). In addition, in the functional level, the spasmolytic effect of β-norlapachone does not involve participation of free radicals, since its curve of relaxation was unchanged in the presence of glutathione, an antioxidant agent." @default.
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- W2107266355 date "2010-10-01" @default.
- W2107266355 modified "2023-10-14" @default.
- W2107266355 title "Synthetic Lapachol Derivatives Relax Guinea-Pig Ileum by Blockade of the Voltage-Gated Calcium Channels" @default.
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- W2107266355 doi "https://doi.org/10.1515/znc-2010-9-1016" @default.
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