1970 Volume 39 Issue 1 Pages 33-47
Reliability of the screening method employing the footpads of mice in the search for antileprous drugs had mainly been evaluated in the use of drugs which had already been established to be effective in the treatment of leprosy, tuberculosis or malarial disease, or otherwise, in the use of some masked compounds of DDS, which were expected to be longer-active and also lower-toxic than DDS.
In the present study, however, the authors employed, in addition, some compounds which had not been clinically tested on mycobacterial diseases, together with some of 60 compounds which have been newly synthesized and consisted of three series.
Each was given orally to the mice, mixed in the diet at concentrations of 0.1 mg or 0.5mg/g, or injected intramuscularly in a corresponding dosage into the dorsal muscle once a week.
The strains of leprosy bacilli employed were N Aneta P2 or B 2409 P12, and the transmission was carried out to inject one of the strain into both of the hind footpads of the experimental mice. The bacterial growth was examined by counting bacilli in each slice of the foot pad covering a period of approximately eight months. A serious deviation in the bacterial counts was observed within a group. However, in most cases, the bacterial counts in the right and the left hind foot pads of each mouse were comparable.
As exceptional cases, the results of INAH, 1314 TH, and Ethambutol were contradictory to their respective clinical findings, and s-DDS, the chemical structure of which is.similar to DDS, and especially to Promacetin, was inff ective, though the results stated in this report are merely based on the continuous method.
To elucidate the origin of such a contradication, the concentrations of these exceptional case drugs in the footpads or in the blood of mice were measured by a radio-tracer techique. When based on the results of this experiment, the relative difficulty of these drugs to arrive in the footpads of mice was supposed to not play an important partt in the effectiveness of these drugs in the footpad method. Therefore, this contradiction may be caused by a difference between the mode of action of a drug against the parasitic leprosy bacilli in the macrophages of the footpads of mice and that in the human lepra cells. The Aryl Propiolthieanilides are considered to be promising.
Subsequent to this study, various kinds of compounds untested on any infections or newly synthesized, together with numerous antibiotics, will be tested by the mouse footpad method in the next stage.
