Pharmacologic implications of alpha-adrenoreceptor interactive parameters for epinephrine enantiomers in the rat vas deferens.
After alkylation of a fraction of the total alpha-adrenoreceptors by phenoxybenzamine in rat vas deferens, the dissociation constants of (-)- and (+)-epinephrine in functional studies were 7 X 10(-7) M and 2 X 10(-5) M, respectively. In the adrenoreceptor-containing tissue fraction, when 3H-labeled WB4101 was used as the interacting ligand, for each enantiomer two affinity sites were found. Only the low-affinity dissociation constant for each isomer correlates with the constant obtained from the functional studies. If the change in Gibb's free energy, delta G degrees, is calculated from the low-affinity binding constants, the values -8.1 and -6.2 kcal/mol for (-)- and (+)-isomer, respectively, are obtained. The small difference in the value between isomers is consistent with the view that the benzylic hydroxyl group of the (-)-isomer forms a hydrogen bond with the receptor. The interaction of epinephrine with this receptor appears to be driven largely by the entropy of the drug-receptor interaction with only a small nonstereoselective contribution from the enthalpy of interaction.
Rice
P J
PJ
College of Pharmacy, Ohio State University, Columbus 43210.
Miller
D D
DD
Sokoloski
T D
TD
Patil
P N
PN
D000818:Animals; D001667:Binding, Competitive; D004146:Dioxanes / Q000378:metabolism; D004837:Epinephrine / Q000493:pharmacokinetics / Q000494:pharmacology*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013237:Stereoisomerism; D013816:Thermodynamics; D014649:Vas Deferens / Q000187:drug effects
D004146:Dioxanes; D008024:Ligands; D011506:Proteins; D011942:Receptors, Adrenergic, alpha; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D004837:Epinephrine