Interventions for Tuberculosis Control and Elimination 2002

longed respiratory depression following curare-like drugs, such as pancuronium,
414 succinylcholine or tubocuronium 415 or non-depolarizing relaxants
such as diallyl-nortroxiferine. 416
Effect of drug opposed by streptomycin: None identified.
Thioacetazone
Discovery. Freund and Schander synthesized benzaldehyde-semicarbazone
in 1896 and 1902, respectively. 417,418 From this basic compound, derivatives
with anti-tuberculosis properties were later developed. After investigations
on sulphonamides had revealed that thiazoles and thiodiazole derivatives
exerted some activity against mycobacteria, 419 Domagk and
collaborators at the Bayer Laboratories synthesized a new class of drugs,
the thiosemicarbazones, of which thioacetazone (figure 25) was shown to
be active against tubercle bacilli. 420
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Figure 25. Chemical structure of thioacetazone, synthesized by Domagk and collaborators
in 1946. 420
Among the numerous derivatives of semicarbazones, three have found particular
activity against M. tuberculosis: 421
p-acetylamino-benzaldehyde-semicarbazone;
p-methoxy-benzaldehyde-semicarbazone;
p-ethylsulfone-benzaldehyde-semicarbazone.
Of these, p-acetylamino-benzaldehyde-semicarbazone, tested under the name
TB I, now known as thioacetazone, became the most widely used semicarbazone.
Activity, mechanism of action and resistance. Thiosemicarbazones, including
thioacetazone, are active only against mycobacteria, and favorable in
vitro and in vivo results against M. tuberculosis were published in 1949. 419
The observed in vitro susceptibility of M. tuberculosis varies considerably,