Studies on Anti-leprotic Agents: Basic Studies on Pyrazine Derivatives for the Chemotherapeutic Agents of Leprosy (First Report)

Abstract

The authors synthesized certain pyrazine derivatives. Each compound was designated as follows and employed in the experiments. (Fig. 1).
For an experiment on their antibacterial actions, the compounds were examined for their effects on Mycobacterium tuberculosis, H37Rv, as compared with the first. The results showed that Pycazid 200 r<, PBS-110 r<, PBS-2 5 r<, diluted soultions, PBS-1 and PBS-2 were effective in checking the growth of H37Rv but the effect of Pycazid was weak.
On acute toxicity to mice, the results of the experiment were as follows.
Pycazid 150.5mg/kg
LD 50 PBS-1 1510.0mg/kg
PBS-2 1540.0mg/kg
The effects of the three compounds on the respiration and blood pressure of rabbits did not show any action to 100ml of 0.02% solution.
No effects was found on the peripheral blood vessels of rabbits to 15ml of each solution (0.02%).
Actions on an excised toad heart; 5-10mg/20ml of PBS-1 and PBS-2 showed no action. But, 1mg/20ml of Pycazid caused an increase of amplitude lasting for minutes. The heart beat become irregular and came to a stillstand at the systolic position with a dose of 20mg/20ml.
Actions on rabbit intestines: The actions of the compounds on the motility and tone of an excised small intestine were tested by the Magnus's method. Neither PBS-1 nor PBS-2 showed any action. The intestinal tone was barely strained with 10mg/20ml of Pycazid, but a gradual decrease caused by application of Pycazid in the tone of the intestine could be antagonized by an after-treatment with BaCl₂.
The spasmogenic activity of acetylcholine was reduced remarkably with the application of Pycazid.
The pharmacological actions and toxicities of PBS-1 and PBS-2 were very weak, PBS-1 and PBS-2 were designated to be used in clinical treatment tests on leprosy.