EFFECTS OF RING FLUORINATION ON THE CARDIOVASCULAR ACTIONS OF DOPAMINE AND NOREPINEPHRINE IN THE DOG

  • 1 January 1980
    • journal article
    • research article
    • Vol. 213  (3) , 509-513
Abstract
The 2-, 5- and 6-fluoro (F) analogs of dopamine (DA) and (.+-.)-norepinephrine (NE) were compared with the respective parent molecules for .alpha., .beta.-1 and .beta.-2 adrenergic and vascular DA activities in pentobarbital-anesthetized dogs. 2-F and 5-F DA were equipotent, while 6-F DA was .apprx. 4-fold less active than DA in causing renal vasodilation in phenoxybenzamine pretreated dogs (vascular DA activity). The 3 analogs were indistinguishable from DA for vasconstrictor activity in the femoral vascular bed (.alpha. adrenergic activity). 2-F and 6-F DA were equipotent to DA, while 5-F was .apprx. 2-fold more active than DA in inotropic activity (.beta.-1 adrenergic activity). F NE analogs showed marked differential activities. 2-F NE resembled isoproterenol in increasing cardiac contractility, lowering diastolic blood pressure and causing vasodialation in the femoral vascular bed. The 5-F analog was the most potent for .beta.-1 adrenergic activity and produced biphasic effects on blood pressure and the femoral vascular bed. 6-F NE exerted no inotropic activity in doses 50- to 80-fold higher than the threshold dose of l-NE and caused vasconstriction. F substitution in either of the 3 positions in the benzene ring of DA induced only minor, if any, difference in receptor activation when compared with DA. F substitution in the benzene ring of NE yielded compounds with marked differential receptor activity. The differences between the effects of F substitution on DA and NE analogs must be related to the only structural difference between the 2 catecholamines, the presence of a .beta.-hydroxyl group in NE.