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Pharmacologic implications of α‐adrenocreceptor interactive parameters for epinephrine enantiomers in the rat vas deferens
Author(s) -
Rice Peter J.,
Miller Duane D.,
Sokoloski Theodore D.,
Patil Popat N.
Publication year - 1989
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530010106
Subject(s) - chemistry , vas deferens , enantiomer , phenoxybenzamine , dissociation constant , alkylation , epinephrine , enthalpy , receptor , stereochemistry , hydrogen bond , medicine , organic chemistry , thermodynamics , biochemistry , molecule , physics , catalysis
After alkylation of a fraction of the total α‐adrenoreceptors by phenoxybenzamine in rat vas deferens, the dissociation constants of (−)‐ and (+)‐epinephrine in functional studies were 7 × 10 −7 M and 2 × 10 −5 M , respectively. In the adrenoreceptor‐containing tissue fraction, when 3 H‐labeled WB4101 was used as the interacting ligand, for each enantiomer who affinity sites were found. Only the low‐affinity dissociation consant for each isomer correlates with the constant obtained from the functional studies. If the change in Gibb's free energy. Δ G °, is calculated from the low‐affinity binding constants, the values −8.1 and −6.2 kcal/mol for (−)‐ and (+)‐isomer, respectively, are obained. The small difference in the value between isomers 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 nonsteroselective contribution from the enthalpy of ineraction.