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 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.
Bass
A S
AS
Department of Pharmacological and Physiological Sciences, The University of Chicago, IL 60637.
Kohli
J D
JD
Adejare
A
A
Kirk
K L
KL
Goldberg
L I
LI
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
D006584:Hexamethonium Compounds; D011941:Receptors, Adrenergic; D004837:Epinephrine