Castiella E, Frechilla D, Lasheras B, Cenarruzabeitia E, Martínez de Irujo J J, Alberdi E, Santiago E, Monge A, Villanueva A, Martinez F J
Department of Pharmacology, Universidad de Navarra, Pamplona, Spain.
J Pharm Pharmacol. 1995 Jul;47(7):601-7. doi: 10.1111/j.2042-7158.1995.tb06722.x.
Cardiotonic effect of 4-(4'-n-butylaniline)-7,8-dimethoxy- 5H-pyrimido[5,4-b]indole (B11) was investigated in isolated cardiac tissue preparations. The action of this agent on force of contraction, beating frequency and cyclic nucleotide phosphodiesterase (PDE) activity was studied. Amrinone was used for comparison. B11 produced concentration-dependent (5 x 10(6)-1 x 10(-4)M) positive inotropic and positive chronotropic responses in guinea-pig atrial tissues. The potency of B11 was greater than that of amrinone. The cardiotonic effects of B11 were not modified by beta-adrenoceptor blockade. Carbachol inhibited the positive inotropic effect of B11. The activity of B11 was increased in desensitized left atrial tissues. B11 inhibited the activities of PDE isoenzymes (type I, II, IV and V) from dog heart ventricle and PDE type IV from guinea-pig heart ventricle nonselectively. It is concluded that B11 possesses potent positive inotropic activity in guinea-pig atria, and the effect is probably mediated by a non-selective inhibition of PDE activity.
研究了4-(4'-正丁基苯胺)-7,8-二甲氧基-5H-嘧啶并[5,4-b]吲哚（B11）对离体心脏组织标本的强心作用。研究了该药物对收缩力、搏动频率和环核苷酸磷酸二酯酶（PDE）活性的作用。使用氨力农作为对照。B11在豚鼠心房组织中产生浓度依赖性（5×10⁻⁶ - 1×10⁻⁴M）的正性肌力和正性变时反应。B11的效力大于氨力农。B11的强心作用不受β-肾上腺素能受体阻断的影响。卡巴胆碱抑制B11的正性肌力作用。B11在脱敏的左心房组织中的活性增加。B11非选择性地抑制犬心室的PDE同工酶（I型、II型、IV型和V型）以及豚鼠心室的PDE IV型的活性。结论是，B11在豚鼠心房中具有强大的正性肌力活性，其作用可能是通过对PDE活性的非选择性抑制介导的。
