Abstract

Studies were directed to measurement of hyperlactic acidemia and hyperglycemia induced by various catecholamines in anesthetized rats and conscious dogs. A family of compounds structurally related to the beta adrenergic blocking agent sotalol (MJ 1999) was investigated for potency with respect to inhibition of the aforementioned metabolic responses. Data were correlated with attenuation of isoproterenol-induced relaxation of isolated guinea-pig tracheal smooth muscle. Increasing the alkyl chain length of the p-alkylsulfonamido moiety on the benzene ring reduced beta adrenergic blocking activity, as did increasing the size of the N-alkyl group on the amino nitrogen up to n-heptyl. Branched N-alkyl groups (e.g., sec.-and tert.-butyl) increased potency. Alpha,. alkyl substitution of the ethanol moiety variably enhanced or lessened beta blocking activity. For the series of compounds, in general, diminution of epinephrine-induced metabolic responses in vivo correlated well with antagonism of isoproterenol-induced relaxation of smooth muscle in vitro. The hyperlactic acidemia response was consistently more sensitive to attenuation (5- to 20-fold) than was the hyperglycemic response.