Allely M C, Ungar A
Br J Pharmacol. 1985 Oct;86(2):393-8. doi: 10.1111/j.1476-5381.1985.tb08908.x.
Propranolol, sotalol and nadolol have been infused into conscious dogs, and doses at which the three drugs are equipotent as beta-adrenoceptor antagonists determined. In euthyroid dogs, sotalol was more effective at lowering heart-rate than an equivalent dose of propranolol, while an equivalent dose of nadolol was without effect. Hyperthyroidism potentiated the lowering of heart-rate by sotalol, but inhibited that by propranolol. The effect of sotalol on heart-rate was correlated with its prolongation of the Q-T interval of the ECG. That of propranolol was correlated with its prolongation of the P-R interval. Nadolol did not affect P-R interval or Q-T interval except at relatively high dosage. We conclude that the tachycardia of hyperthyroidism is not affected by blockade of beta-adrenoceptors and therefore that it is not mediated by adrenergic mechanisms. The effectiveness of propranolol and sotalol in lowering heart-rate must be due to actions peculiar to those drugs, and not to beta-adrenoceptor antagonism.
已将普萘洛尔、索他洛尔和纳多洛尔注入清醒犬体内,并确定了这三种药物作为β肾上腺素能受体拮抗剂的等效剂量。在甲状腺功能正常的犬中,索他洛尔在降低心率方面比同等剂量的普萘洛尔更有效,而同等剂量的纳多洛尔则无效。甲状腺功能亢进增强了索他洛尔降低心率的作用,但抑制了普萘洛尔的这种作用。索他洛尔对心率的影响与其延长心电图的Q-T间期相关。普萘洛尔的影响与其延长P-R间期相关。除相对高剂量外,纳多洛尔不影响P-R间期或Q-T间期。我们得出结论,甲状腺功能亢进的心动过速不受β肾上腺素能受体阻断的影响,因此不是由肾上腺素能机制介导的。普萘洛尔和索他洛尔在降低心率方面的有效性必定归因于这些药物特有的作用,而非β肾上腺素能受体拮抗作用。