RT Journal Article
SR Electronic
T1 CONFORMATIONAL SIMILARITIES BETWEEN MOLECULAR MODELS OF PHENETHYLAMINE AND OF POTENT INHIBITORS OF THE UPTAKE OF TRITIATED NOREPINEPHRINE BY ADRENERGIC NERVES IN RABBIT AORTA
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 158
OP 165
VO 173
IS 1
A1 MAXWELL, R. A.
A1 CHAPLIN, E.
A1 ECKHARDT, S. BATMANGLIDJ
A1 SOARES, J. R.
A1 HITE, G.
YR 1970
UL http://jpet.aspetjournals.org/content/173/1/158.abstract
AB Tricycic antidepressants, deoxypipradrol, methylphenidate and cocaine are competitive inhibitors of the uptake of norepinephrine by rabbit aortic strips. All have pKa. values greater than 8.5 and, therefore, are greater than 90% protonated and positively charged at physiologic pH. These agents can readily take conformations such that one phenyl ring and the protonated nitrogen superimpose over their counterparts in the planar, trans-staggered conformation of β-phenethylamine. In these conformations the inhibitors have a second phenyl ring or a carbomethoxy group extending above the plane of the phenethylamine in the vicinity of the β-carbon of the phenethylamine. Tricyclic antidepressants, cocaine, methylphenidate and deoxypipradrol bear adequate similarities to each other and to β-phenethylamine in regard to pKa, kinetics, structure and conformational possibilities to indicate that they attach to the same "amine pump" receptor site as does norepinephrine. The relative potencies of these agents as inhibitors of uptake of tritiated norepinephrine into rabbit aortic strips have been determined. These agents have sufficient structural and conformational differences to permit a rationale to be developed which explains their differences in potency as inhibitors of the uptake of norepinephrine. © 1970, by The Williams & Wilkins Company