PHARMACOLOGIC POTENCY AND SELECTIVITY OF A NEW BRONCHODILATOR AGENT: SOTERENOL (MJ 1992)

¹ Department of Pharmacology, Mead Johnson Research Center, Evansville, Indiana; Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Soterenol (MJ 1992), a methanesulfonamido-phenethanolamine related structurally to isoproterenol, was a highly effective bronchodilator agent in several animal species by various routes of administration. The bronchodilator potency of soterenol was equivalent to, or greater than, that of isoproterenol; the duration of bronchodilation after soterenol was consistently and significantly greater than that induced by isoproterenol. The latter agent frequently caused a secondary, pronounced increase in pulmonary airway resistance. This phenomenon did not occur after soterenol administration. Cardiovascular responses to soterenol were decidedly less in both cats and dogs than those evoked by equipotent bronchodilator amounts of isoproterenol. Administration of soterenol by intrapulmonic or intraduodenal routes was particularly devoid of cardiovascular involvement. The total pharmacologic evaluation of soterenol indicated a dominant beta adrenergic receptor stimulant effect subserving bronchodilation accompanied by a lesser proportion of alpha adrenergic receptor stimulant action. The latter mechanistic component was not shared by isoproterenol. Large safety margins between effective bronchodilatory dosage and toxic amounts of soterenol were revealed by toxicity studies in guinea pigs and dogs by various routes of administration.