title: Effect of ring fluorination of epinephrine on its cardiovascular adrenoceptor activities.
abstract: Effects of fluorine (F) substitution on the 2- and 6-positions of the catechol ring of epinephrine (Epi) on its alpha- and beta-adrenoceptor agonist activities were studied in anesthetized dogs. Increments in heart rate and contractile force were used as measures of beta 1-adrenoceptor activity, while increases and decreases in blood pressure and decreases and increases in femoral blood flow were used as measures of alpha- and beta 2-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 beta-adrenoceptor agonist with little agonist activity at alpha-adrenoceptors, while the 6-F analog was a selective a-adrenoceptor agonist with no significant beta-adrenoceptor effects. Of added significance, 2-FEpi was more potent than Epi as a beta 1-adrenoceptor agonist, while 6-F Epi was more potent than the parent compound as an alpha-adrenoceptor agonist. The possible mechanisms for the effects of ring fluorination on the adrenoceptor activities of Epi and other sympathomimetic amines are discussed.
authors: Department of Pharmacological and Physiological Sciences, The University of Chicago, IL 60637.
authors: A S
authors: AS
authors: Bass
authors: J D
authors: JD
authors: Kohli
authors: A
authors: A
authors: Adejare
authors: K L
authors: KL
authors: Kirk
authors: L I
authors: LI
authors: Goldberg
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005269:Femur / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D006584:Hexamethonium Compounds; D011941:Receptors, Adrenergic; D004837:Epinephrine