新しいβ受容体遮断薬，befunololとindenololの膜安定化作用

Membrane Stabilizing Actions of Befunolol and Indenolol, New β-Adrenergic Receptor Blocking Drugs

　β受容体遮断薬のあるものは強いキニジン様抗不整脈作用を示すことが知られている。実験的不整脈に対するβ受容体遮断薬の拮抗作用のうちで，カテコラミン不整脈に対する場合は別にして，たとえばジギタリス誘発性不整脈への拮抗については，こうしたβ遮断薬のキニジン様作用が重要な役割を果たしているという見解もある^1,2）。現在のところ，β遮断薬の臨床的抗不整脈作用におけるキニジン様作用の意義を疑問視する立場も多いが^3,4），心臓組織のある病的状態，たとえば心筋虚血などにおいては，それら薬物のβ受容器遮断作用とは別に，キニジン様作用が効果を現わすことはありえないことではない^5,6）。またキニジン様作用を主体としたclass−1型抗不整脈剤（quinidine^7），lidocaine^7），procaine amide^8））の示す電気生理学的特徴のひとつに，活動電位最大立ち上がり速度を刺激頻度依存的に抑制することが挙げられる。

　Membrane stabilizing actions of befunolol and indenolol, new B-adrenergic blockers, on the electrical activities were investigated in the guinea pig myocardium using glass microelectrodes and the frog sciatic nerve using sucrose gap method. Both the drugs reduced maximum upstroke velocity (Vmax) and Over Shoot of cardiac action potentials dose-dependently without affecting resting membrane potential. The drugs did not prolong rerfactory period, but increased the ratio refractory period/action potential duration. Reduction of Vmax in the presence of the drugs was produced rate-dependently at the rates between 0.25 and 5 Hz. The rate-dependence was derived presumably from retardation of the recovery kinetics of Vmax during diastole from the drug-induced suppression of the Na-system. In the frog nerve, the drugs also exerted local anesthetic action (reduction in the height of compound action potentials), and indenolol, but not befunolol, was as potent as lidocaine. In addition, the local anesthetic activity of indenolol, like that of lidocaine, was increased when higher rates of stimulation were applied.