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• W2004187410 abstract "CP-060S, (−)-(S)-2-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-3-[3-[N-methyl-N-[2-(3,4-methylenedi-oxyphenoxy)methyl]amino]propyl]-1,3-thiazolidin-4 hydrogen fumarate, is a novel cardioprotective drug which is designed to prevent Ca2+ overload and cause vasorelaxation. The effects of this compound were evaluated and compared with those of CP-060R (enantiomer of CP-060S,) and diltiazem (Ca2+ channel antagonist) in a veratridine-induced model of Ca2+ overload and vasorelaxation. After 5-min superfusion of veratridine (74 μM), intracellular free calcium concentrations ([Ca2+]i) of rat single cardiomyocytes, as measured with the fura-2 procedure, were greatly elevated, from 44 ± 5 nM to 3705 ± 942 nM, and subsequently generated cell contracture. Pretreatment of cardiomyocytes with more than 300 nM of CP-060S or CP-060R for 30 min provided almost complete protection against the veratridine-induced cell contracture; in CP-060S(1 μM-treated myocytes, [Ca2+]i were minimal and partially elevated from 42 ± 5 nM to 72 ± 14 nM after 5 min of veratridine superfusion. In comparison, diltiazem showed no protection below 1 μM and only partial protection at 10 μM. CP-060S, CP-060R and diltiazem all shifted the concentration-response curve for CaCl2 to the right in a competitive manner in depolarized rat thoracic aorta. The pA2 values of CP-060S, CP-060R and diltiazem were 9.16 ± 0.18, 8.24 ± 0.14 and 7.66 ± 0.09, respectively. Our results indicate that CP-060 behaves stereoselectively as a Ca2+ channel antagonist and non-stereoselectively to protect against veratridine-induced contracture. The latter effect suggests that Ca2+ entry blockade is not the mechanism by which CP-060S exerts cardioprotection." @default.
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• W2004187410 date "1996-09-01" @default.
• W2004187410 modified "2023-09-25" @default.
• W2004187410 title "Actions of CP-060S on veratridine-induced Ca2+ overload in cardiomyocytes and mechanical activities in vascular strips" @default.
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• W2004187410 doi "https://doi.org/10.1016/0014-2999(96)00460-8" @default.
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