1 The dissociation constants of 5-hydroxytryptamine and 5-hydroxy-N,N-dimethyltryptamine have been measured and the zwitterion constants have been estimated from the pKas of analogous methoxyamines and the phenolic quaternary ammonium salt. 2 Direct measurement of zwitterion constants has been made by a spectroscopic method which has been used also with several phenolic amines previously studied electrometrically. It makes fewer assumptions and so should be more reliable but an appraisal of the methods available indicates that none can be singled out as being best and it is desirable to obtain results with as many as possible. 3 The results consolidate previous observations on the relations between chemical structure and zwitterion constant; possibly zwitterions are stabilizId by any factor which stabilizes water structure.Dimethylamino compounds have lower zwitterion constants than their methylamino or aminoanalogues but there is no reason to doubt the previous finding that diethylamino compounds have higher zwitterion constants than their dimethylamino analogues. 4 The proportion of 5-hydroxytryptamine present as the neutral molecule or zwitterion in physiological conditions is small; however, with dopamine, the proportion present as the zwitterion could be as much as 10%.

1 Coryneine is 2.7 times as active as cinobufotenine on the frog rectus but on the guinea-pig ileum cinobufotenine is 1.5 times as active as coryneine. Cinobufotenine is a potent stimulant of parasympathetic ganglia and its effects are competitively antagonized by hexamethonium. 2 The effects of pH on activity relative to a standard whose ionisation is constant (Me4N or the trimethylammonium analogue of tryptamine) are consistent with the phenate form being weaker than the phenolic form but the changes are smaller than with coryneine because cinobufotenine is a weaker acid. 3 The hydroxyl group makes a large contribution to activity. Cinobufotenine is 9 times as active as the analogue without a hydroxyl on the frog rectus and 12 times as active as it on the ileum. The 5-methoxy analogue is an antagonist on the frog rectus and a very weak partial agonist on the ileum. 4 Cinobufotenine and the quaternary derivative of tryptamine have less than one-thousandth of the activity of 5-hydroxytryptamine on the rat fundus strip.