Okumura K, Ichihara K, Nagasaka M, Oda N, Tajima K
New Drug Research Laboratory, Maruko Pharmaceutical Co., Ltd., Kasugai, Japan.
Eur J Pharmacol. 1993 Apr 22;235(1):69-74. doi: 10.1016/0014-2999(93)90821-x.
The Ca2+ entry blocking effects of MPC-1304, a new Ca2+ entry blocker of the 1,4-dihydropyridine type, and of its (S) and (R) enantiomers and metabolites were examined on Ca(2+)-induced contractions in isolated rabbit arteries. The Ca2+ entry blocking activity of the (S) enantiomer of MPC-1304 was approximately 150 times greater than that of its (R) enantiomer. Likewise, the antihypertensive effect of the (S) enantiomer was twice as great as that of MPC-1304 (racemate) in conscious spontaneously hypertensive rats, while the (R) enantiomer was ineffective. Thus, most of the pharmacological activity of MPC-1304 resides in its (S) configuration. The main metabolic products of MPC-1304 also inhibited the Ca(2+)-induced contraction in the isolated vascular smooth muscles. These active metabolites showed a stereoselectivity similar to that of MPC-1304 for Ca2+ entry blocking activity, and may contribute to the potent antihypertensive action of MPC-1304.
研究了新型1,4 - 二氢吡啶类钙通道阻滞剂MPC - 1304及其（S）和（R）对映体与代谢产物对离体兔动脉中Ca(2 +)诱导收缩的钙内流阻断作用。MPC - 1304的（S）对映体的钙内流阻断活性约为其（R）对映体的150倍。同样，在清醒自发性高血压大鼠中，（S）对映体的降压效果是MPC - 1304（消旋体）的两倍，而（R）对映体则无效。因此，MPC - 1304的大部分药理活性存在于其（S）构型中。MPC - 1304的主要代谢产物也抑制离体血管平滑肌中Ca(2 +)诱导的收缩。这些活性代谢产物在钙内流阻断活性方面表现出与MPC - 1304相似的立体选择性，可能有助于MPC - 1304的强效降压作用。
