LABORATORY STUDIES ON JOINT EFFECTS OF CERTAIN TRIS (P-AMINOPHENYL) CARBONIUM SLATS AND ANTIMONIALS AS ANTISCHISTOSOMAL DRUGS

Abstract

Tris(p-aminophenyl) carbonium (TAC) pamoate and antimonials, such as tartar emetic and stibophen, have broad antischistosomal activity in animals and man, but both groups have important limitations. Thus the slow-acting TAC pamoate must be given for several weeks to obtain a high degree of effect and the fast-acting antimonials have a narrow therapeutic index. This study deals with whether TAC pamoate and antimonials together have a useful degree of joint action against Schistosoma mansoni without commensurate joint toxicity for the host. A marked degree of synergism in antischistosomal activity occurred with relatively low amounts of TAC pamoate and tartar emetic or stibophen in vitro and in infected mice, particularly when TAC pamoate was started ahead of the antimonial. Moreover, neither TAC pamoate nor tartar emetic affected appreciable the gross toxicity of the other for normal mice. An encouraging degree of joint antischistosomal action by TAC pamoate and tartar emetic also occurred in infected rhesus monkeys. The results suggest that the use of TAC pamoate and antimonials together may avoid some of their main limitations when used alone.