ACTIONS OF 5-(1,3-DIMETHYLBUTYL)-5-ETHYL BARBITURIC ACID, PENTOBARBITAL, AMOBARBITAL AND THIOPENTAL ON THE SINO-ATRIAL NODAL ACTIVITY OF THE ISOLATED HEART

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The convulsant barbiturate, sodium 5-(1,3-dimethylbutyl)-5-ethyl barbiturate (DMBEB) exerts a dual action on isolated spontaneously beating guinea pig atria suspended in Krebs-Henseleit solution at 37°C. At concentrations from 0.001 to 0.01 mg/ml, it has predominantly a transient rate-increasing effect, whereas at higher concentrations an additional negative chronotropic action appears. Experiments with atria of reserpinepretreated guinea pigs (3 mg/kg, 24 hr) and experiments with beta receptor blockade have shown that the rate-increasing effect of DMBEB is not mediated by released norepinephrine and that DMBEB probably has no direct action on adrenergic beta receptors. Sodium pentobarbital and sodium amobarbital, though structurally related to DMBEB, exhibit exclusively a negative chronotropic action. Their negative chronotropic effect is identical; it occurs in the same concentration range in which DMBEB manifests its rate-decreasing effect on the sino-atrial node. Sodium thiopental is more potent in its rate-decreasing effect than are sodium pentobarbital and sodium amobarbital.