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Antisera to debrisoquin, a widely used anti-hypertensive agent, have been obtained from rabbits following immunization with a conjugate of 4-[1,2,3,4-tetrahydroisoquinolin-2-yl)(imino)-methylamino] butanoic acid and bovine serum albumin. Employing tritium labelled debrisoquin as the radioligand for the antisera, a radioimmunoassay (RIA) was developed which allows for the specific determination of the drug directly in plasma. After logit transformation, a linear calibration line was obtained between 0.1 to 10 ng of unlabelled debrisoquin. The 4, 5, 6, 7 and 8-hydroxy derivatives of debrisoquion, known metabolites in man, showed less than 1.5% cross-reaction with the antisera. The specificity of the RIA was established when good agreement was obtained for the levels of debrisoquin in patients' plasma using the RIA and a specific GC/MS method. The simplicity of the RIA makes this method attractive for the routine clinical monitoring of the plasma levels and/or experimental protocols in which high sample throughput is required.

A number of indoles containing the 2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl side chain have been prepared by standard methods. Alternate, novel syntheses of indole-2-carboxamides and indole-2-carbonitriles have been developed. The title compound, 7e, was found to be a potent inhibitor of bovine prostaglandin synthetase in vitro and to lower serum prostaglandin levels after oral or intraperitoneal administration to rats. Consistent with prostaglandin synthetase inhibition, 7e prevented arachidonic acid induced diarrhea in mice and also collagen, ADP, or epinephrine induced platelet aggregation in human platelet-rich plasma. In contrast to many prostaglandin synthetase and platelet-aggregation inhibitors, 7e had neither ulcerogenicity nor systemic antiinflammatory activity in rats.