QUINTERENOL, A NEW BETA ADRENERGIC STIMULANT

¹ Department of Pharmacology, Chas. Pfizer & Co., Inc., Groton, Connecticut

Quinterenol (1-[5-(8-hydroxyquinolyl]-2-isopropylaminoethanol) antagonized histamine-, acetylcholine-and serotonin-induced bronchoconstriction and prevented egg albumin-induced anaphylaxis in guinea pigs. Orally and by inhalation quinterenol was as potent as isoproterenol; by i.v. and s. c. routes it was less potent. The onset of action was slower and the duration of action was considerably longer for quinterenol than for isoproterenol. In dogs, quinterenol, 0.5 mg/kg i.v., increased heart rate, cardiac output and stroke volume and lowered peripheral vascular resistance. In dog open chest preparations quinterenol increased cardiac output without elevating myocardial oxygen consumption and lowered blood pressure without reducing coronary arterial blood flow. In dog hind limb preparations quinterenol increased femoral arterial blood flow; in this respect it was as potent as papaverine, but it had considerably longer duration of action. All cardiovascular effects of quinterenol were blocked by propranolol. Chlorpromazine blocked quinterenol-induced tachycardia, but not the hypotensive effect. Quinterenol-induced cardiac acceleration in dogs was not abolished by vagotomy and sectioning of the spinal cord at the level of the second cervical vertebra, or by pretreatment with reserpine. Quinterenol relaxed isolated guinea-pig tracheal strips and abolished the spontaneous contractile activity of isolated rat uteri. These effects were antagonized by propranolol. At single doses up to 4 mg quinterenol had no positive inotropic or chronotropic effects on isolated perfused hearts of various species; it had no positive inotropic activity on isolated cat heart papillary muscles at concentrations up to 10^-5 g/ml. The data indicated that the positive chronotropic effect of quinterenol is probably not due to its direct interaction with beta adrenergic receptors.