Armstrong J, Barlow R B
Br J Pharmacol. 1976 Aug;57(4):501-16. doi: 10.1111/j.1476-5381.1976.tb10377.x.
The dissociation constants of many phenolic amines, including benzylamines, phenethylamines, phenylethanolamines, phenylpropylamines, catecholamines, and apomorphine have been measured by potentiometric titration at 25 degrees 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 degrees 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 pKa were not constant and found to increase with increasing concentration. The range studied was usually 5-15 mM and a least-squares line-fit, based on the empirical assumption that pKa varies with (concentration)1/2, has been used to calculate values for 10 mM solutions and to extrapolate to infinite dilution and to 100 mM. The dependence of pKa on concentration was much less at 37 degrees C than at 25 degrees C. 3 At 37 degrees C the pKa 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 pKa 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 alpha-adrenoceptors and probably not with activity at beta-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.
包括苄胺、苯乙胺、苯乙醇胺、苯丙胺、儿茶酚胺和阿扑吗啡在内的许多酚胺类化合物的解离常数，已在25℃下通过电位滴定法进行了测定。对它们的许多甲氧基衍生物以及一系列酚季铵盐也进行了测量。部分化合物还在37℃下进行了研究。2通常每种化合物至少进行五次滴定，并应用德拜-休克尔理论将浓度转换为活度，但pKa的估计值并不恒定，且发现其随浓度增加而增大。研究的浓度范围通常为5-15 mM，基于pKa随（浓度）1/2变化的经验假设，采用最小二乘线性拟合来计算10 mM溶液的值，并外推至无限稀释和100 mM。pKa对浓度的依赖性在37℃时比在25℃时小得多。3在37℃时，该组中许多具有生物学意义的化合物，如多巴胺、去甲肾上腺素、肾上腺素和异丙肾上腺素、可卡因（多巴胺的三甲基铵衍生物）和阿扑吗啡的pKa值在生理pH的1个对数单位范围内，这表明两性离子或不带电荷的酚胺存在相当大的比例。4已根据酚胺及其甲氧基和季铵三甲基铵类似物的pKa值估算了两性离子常数。两性离子的形成似乎与α-肾上腺素受体的活性无关，可能也与β-受体的活性无关。活性物种似乎可能含有未电离的酚基团，但在多巴胺受体处，这可能存在于不带电荷的酚胺中，而不是酚铵盐中。
