COMPARISON OF THE BETA RECEPTOR BLOCKING PROPERTIES OF TWO ANALOGS OF DICHLOROISOPROTERENOL (DCI)

¹ Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas

The beta receptor blocking properties of 1-(2',4'-dichlorophenyl)-2-isopropylaminoethanol (2,4-DCI) and 1-(2', 4'-dichlorophenyl)-2-t-butylaminoethanol (DCB) were determined in the anesthetized cat. Additional studies with DCB were conducted in anesthetized dogs. Both compounds blocked cardiac and vascular beta receptors in the cat at threshold doses of 0.03 mg/kg for DCB and 3 mg/kg for 2,4-DCI. Neither compound exerted significant intrinsic sympathomimetic or myocardial depressant activity. In dogs, DCB treatment reduced the fall in diastolic pressure, the positive inotropic effect, the positive chronotropic effect and the increase in femoral arterial blood flow induced by isoproterenol in the same dose range. No significant intrinsic sympathomimetic or myocardial depressant effects were evoked even after large doses of DCB. Placing the Cl groups at the 2,4 positions appears to eliminate the intrinsic sympathomimetic and myocardial depressant properties that are produced by the 3,4 substituted analog, dichloroisoproterenol (DCI). Substitution of a tertiary butyl group for an isopropyl group on the N of the ethanolamine side chain increases beta receptor blocking potency. Both DCB and 2,4-DCI were nonselective in exerting their beta receptor blocking effects on the parameters studied.