Selective Blockade of Adrenoceptive Beta Receptors in the Heart

On the basis of a study of the activity of five sympathomimetic amines, Ahlquist in 1948 classified adrenoceptive receptors into two main types, which he designated alpha and beta. This classification has been vindicated by the development of drugs which specifically block the effects of stimulation of one type of receptor but not the other. Classical adrenergic blocking drugs such as phenoxybenzamine, dibenamine, phentolamine, tolazoline and dihydroergotamine block the effects of stimulation of alpha receptors but not beta receptors (Nickerson, 1949; Levy Moran in each case the side chain is identical with that of isoprenaline, or as in the last three com- pounds differs by the addition of an -OCH2 group. The blocking activity of these com- pounds is similar qualitatively, in that they block all beta receptors, but differs quantitatively. Another group of compounds, which block some but not all beta receptors, has recently emerged. These compounds include N-isopropylmethoxamine (Levy, 1964) which blocks beta receptors in the rat uterus; N tertiary butylmethoxamine (Levy, 1966a), and dimethyl isopropylmethoxamine (Levy, 1966b) which block beta receptors in the rat uterus, canine intestine and peripheral blood vessels. None of these compounds blocks the cardiac inotropic or chronotropic actions of cate- cholamines. Structurally these compounds are characterized by having a methyl group attached to the alpha carbon atom of the side chain. These observations suggest that beta receptors are not a homogenous group and may be capable of division into sub-groups. This hypothesis is further substantiated by the present paper in which