I 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 370C. 2 Usually at least five titrations were made with each compound and Debye-Huckel 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 pK5 varies with (concentration)"12, 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 370C than at 25°C. 3 At 370C 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 a-adrenoceptors and probably not with activity at P-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.

1 Vasodepressor effects of prostacyclin (5z-5,6-didehydro-9-deoxy-6,9a-epoxyprostaglandin F1) and its decomposition product 6-oxo-prostaglandin F1l, (6-oxo-PGF1,,) have been compared with those of prostaglandin E2 (PGE2) in anaesthetized rats and rabbits. 2 In rats intravenous prostacyclin produced hypotension and was 4-8 times more potent than PGE2 and about 128 times more potent than 6-oxo-PGF1,.3 In rabbits also, intravenous prostacyclin (less than 2 ug/kg) produced hypotension and was twice as active as PGE2 and approximately 250 times more active than 6-oxo-PGF1a,. 4 In rats and rabbits vasodepressor responses induced by prostacyclin were similar in magnitude after either intravenous or intra-aortic administration. 5 Thus, in both species prostacyclin resembles PGE2 in producing vasodepression but does not lose activity on passage through the lungs. The results emphasize the need to consider prostacyclin in addition to PGE2 as a major determinant influencing blood pressure.

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