Briand V, Laurent S, Tsoucaris-Kupfer D, Legrand M, Brisac A M, Schmitt H
Laboratoire de Pharmacologie Cardiovasculaire, INSERM U 228, Paris, France.
Eur J Pharmacol. 1988 May 20;150(1-2):43-50. doi: 10.1016/0014-2999(88)90748-0.
The negative inotropic effects and the central and peripheral hypotensive effects of (+) and (-) PN 200-110 were investigated in cultured chick heart cells and in spontaneously hypertensive rats, respectively. There was a large difference in negative inotropic potency between the two enantiomers in cultured chick embryo ventricular cells: the (+) enantiomer was 140 fold more potent (IC50 = 1.1 +/- 0.2 nM) than the (-) enantiomer (IC50 = 160 +/- 20 nM). (+) PN 200-110 was 10 fold more potent than (-) PN 200-110 in lowering blood pressure after intravenous injection and only three fold more potent after intra-cerebroventricular injection (i.c.v.) into pentobarbital-anaesthetized spontaneously hypertensive rats. I.c.v. administered (+) PN 200-110 (1 microgram/kg) partially antagonized the hypertensive response to i.c.v. administered BAY K 8644 (30 micrograms/kg), a calcium channel agonist, while the same dose of the (-) enantiomer did not change the i.c.v. BAY-induced increase in blood pressure. These results suggest that the dihydropyridine calcium channel antagonist, PN 200-110, may act centrally and stereoselectively at the level of the dihydropyridine receptor sites involved in the control of blood pressure in spontaneously hypertensive rats.
分别在培养的鸡心脏细胞和自发性高血压大鼠中研究了（+）和（-）PN 200 - 110的负性肌力作用以及中枢和外周降压作用。在培养的鸡胚心室细胞中，两种对映体的负性肌力效力存在很大差异：（+）对映体的效力（IC50 = 1.1 +/- 0.2 nM）比（-）对映体（IC50 = 160 +/- 20 nM）强140倍。静脉注射后，（+）PN 200 - 110降低血压的效力比（-）PN 200 - 110强10倍，而在戊巴比妥麻醉的自发性高血压大鼠脑室内注射（i.c.v.）后，效力仅强3倍。脑室内注射（+）PN 200 - 110（1微克/千克）部分拮抗了对脑室内注射钙通道激动剂BAY K 8644（30微克/千克）的升压反应，而相同剂量的（-）对映体并未改变脑室内注射BAY诱导的血压升高。这些结果表明，二氢吡啶钙通道拮抗剂PN 200 - 110可能在中枢以立体选择性方式作用于参与自发性高血压大鼠血压控制的二氢吡啶受体部位。
