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THE IONIZATION OF PHENOLIC AMINES, INCLUDING APOMORPHINE, DOPAMINE AND CATECHOLAMINES AND AN ASSESSMENT OF ZWITTERION CONSTANTS
Author(s) -
ARMSTRONG J.,
BARLOW R.B.
Publication year - 1976
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1976.tb10377.x
Subject(s) - zwitterion , chemistry , potentiometric titration , dissociation constant , apomorphine , isopropylamine , activity coefficient , phenethylamines , medicinal chemistry , stereochemistry , organic chemistry , aqueous solution , agonist , receptor , molecule , ion , biochemistry
1 The dissociation constants of many phenolic amines, including benzylamines, phenethylamines, phenylethanolamines, phenylpropylamines, catecholamines, and apomorphine have been measured by potentiometric titration at 25°C. Measurements have also been made with many of their methoxy derivatives and with series of phenolic quaternary ammonium salts. Some compounds were also studied at 37°C. 2 Usually at least five titrations were made with each compound and Debye—Hückel theory was applied to convert concentrations to activities but the estimates of pK a were not constant and found to increase with increasing concentration. The range studied was usually 5–15 m m and a least‐squares line‐fit, based on the empirical assumption that pK a varies with (concentration) 1/2 , has been used to calculate values for 10 m m solutions and to extrapolate to infinite dilution and to 100 m m . The dependence of pK a on concentration was much less at 37°C than at 25°C. 3 At 37°C the pK a values of many biologically interesting compounds in the group, dopamine, noradrenaline, adrenaline and isoprenaline, coryneine (the trimethylammonium derivative of dopamine) and apomorphine are within 1 log unit of physiological pH, indicating the presence of a significant proportion of either the zwitterion or of the uncharged phenolic amine. 4 Zwitterion constants have been estimated from the pK a values of the phenolic amines and those of their methoxy and quaternary trimethylammonium analogues. Zwitterion formation does not appear to be associated with activity at α‐adrenoceptors and probably not with activity at β‐receptors. The active species seems likely to contain the unionised phenolic group but at dopamine receptors this may be in the uncharged phenolic amine rather than in the phenolic ammonium salt.