The ion-pair extraction, purification, and liquid chromatographic analysis of indolealkylamines in human urine.

A highly efficient ion-pair extraction technique for the isolation of tryptamine, 5-hydroxytryptamine, and their mono- and N,N-dimethylated derivatives from aqueous media is described. The technique has been used to isolate nanogram quantities of both N, N-dimethyltryptamine and 5-hydroxy-N, N-dimethyltryptamine from large volumes of urine. A rapid and efficient normal-phase liquid chromatographic procedure has also been developed for the subsequent purification of indolealkylamines isolated from urine. The methods described have been used in the measurement of the urinary excretion of 5-hydroxy-N, N-dimethyltryptamine. Analyses were performed by liquid chromatography using a cation-exchange column with online fluorescence detection. Further characterization was achieved by stop-flow spectroscopic analysis of the LC eluant.

Structure-activity relationships of clonidine- and tolazoline-like compounds at histamine and alpha-adrenoceptor sites.

1 Thirty clonidine- and tolazoline-like compounds with differing phenyl ring substituents were tested for agonistic actions at histamine H1-receptors (guinea-pig ileum), histamine H2-receptors (guinea-pig driven right ventricular strips), post-junctional alpha-adrenoceptors (rat desheathed was deferens) and pre-junctional alpha-adrenoceptors (inhibition of sympathetic stimulation in guinea-pig driven left atria). 2 All compounds were inactive at histamine H1-receptors, while 21 of the 30 compounds displayed varying stimulant activity at H2-receptors. 3 At post-junctional alpha-receptors all 30 compounds produced stimulant actions, whereas at prejunctional alpha-receptors the compounds displayed either agonistic or antagonistic actions. 4 Thus structure-activity-relationships (SAR) could only be validated for histamine H2- and post-junctional alpha-receptor effects. These studies show that the most potent compounds are those with 2,6-phenyl substituents in which rotation is restricted so that the two rings are aplanar. Electronic effects of the substituents have a greater influence on activity at H2- than at alpha-receptors. 5 The major difference in SAR involves the influence of substituents in the 3, 4 or 5 positions on the phenyl ring. The presence of these substituents abolish significant activity at H2-receptors, while alpha-receptor stimulant activity is retained.