Gross R, Kayser M, Schramm M, Taniel R, Thomas G
Arch Int Pharmacodyn Ther. 1985 Oct;277(2):203-16.
The hemodynamic effects of the dihydropyridine-derivative BAY K 8644 (methyl-1,4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoro-methylphenyl)-pyridine-5-carboxylate), a chemical analogue of Nifedipine, were evaluated in 9 conscious, chronically instrumented dogs. Compared to Nifedipine, BAY K 8644 displays an opposite pharmacological profile. Dose-dependent hemodynamic effects are observed at doses of 4 micrograms/kg i.v. and above. With 32 micrograms/kg i.v. BAY K 8644 increases total peripheral vascular resistance by 100%. It causes a rise of both, systolic and diastolic, blood pressure up to 196/138 mm Hg at spontaneous sinus rhythm and up to 216/162 mm Hg when keeping heart rate constant at 150 beats/minute. Spontaneous heart rate reflexly drops to 52 beats/minute. Cardiac contractility as indicated by LV(dP/dt)max markedly increases from 2800 to 5600 mm Hg/s at spontaneous sinus rhythm and from 2900 to 6100 mm Hg/s while pacing at 150 beats/minute. These effects are apparently neither affected by alpha-adrenergic blockade with Phenoxybenzamine (5 mg/kg i.v.) nor by beta-blockade with Propranolol (0.5 mg/kg i.v.) but can be reserved by equivalent doses of Nifedipine. In conclusion, the Calcium-agonistic dihydropyridine BAY K 8644 due to its novel mechanism of action could be the precursor of a new class of positive inotropic or antihypotensive drugs.
在9只清醒、长期植入仪器的犬中评估了二氢吡啶衍生物BAY K 8644（甲基-1,4-二氢-2,6-二甲基-3-硝基-4-(2-三氟甲基苯基)-吡啶-5-羧酸酯）的血流动力学效应，它是硝苯地平的化学类似物。与硝苯地平相比，BAY K 8644表现出相反的药理学特征。静脉注射剂量为4微克/千克及以上时可观察到剂量依赖性血流动力学效应。静脉注射32微克/千克的BAY K 8644可使总外周血管阻力增加100%。在窦性心律时，它可使收缩压和舒张压分别升高至196/138毫米汞柱，在心率保持恒定为150次/分钟时可升高至216/162毫米汞柱。窦性心律自发下降至52次/分钟。左心室最大dp/dt所表示的心脏收缩力在窦性心律时从2800显著增加至5600毫米汞柱/秒，在以150次/分钟起搏时从290起增加至6100毫米汞柱/秒。这些效应显然既不受苯氧苄胺（静脉注射5毫克/千克）的α-肾上腺素能阻断影响，也不受普萘洛尔（静脉注射0.5毫克/千克）的β-阻断影响，但可被等量的硝苯地平逆转。总之，钙激动剂二氢吡啶BAY K 8644由于其新的作用机制可能成为一类新型正性肌力或抗低血压药物的前身。
