EFFECT OF RING FLUORINATION OF EPINEPHRINE ON ITS CARDIOVASCULAR ADRENOCEPTOR ACTIVITIES

Effects of fluorine (F) substitution on the 2-and 6-positions of the catechol ring of epinephrine (Epi) on its α-and β-adrenoceptor agonist activities were studied in anesthetized dogs. Increments in heart rate and contractile force were used as measures of β1-adrenoceptor activity, while increases and decreases in blood pressure and decreases and increases in femoral blood flow were used as measures of α- and β2-adrenoceptor activities, respectively. F substitution on the 2- and 6-positions of the catechol ring yielded compounds with opposite receptor selectivities: 2-FEpi was a selective β-adrenoceptor agonist with little agonist activity at α-adrenoceptors, while the 6-F analog was a selective a-adrenoceptor agonist with no significant β-adrenoceptor effects. Of added significance, 2-FEpi was more potent than Epi as a β1-adrenoceptor agonist, while 6-F Epi was more potent than the parent compound as an α-adrenoceptor agonist. The possible mechanisms for the effects of ring fluorination on the adrenoceptor activities of Epi and other sympathomimetic amines are discussed. © 1990.