THE CONVULSIVE ACTION OF 2,5-DICARBETHOXY 3,4-DIHYDROXYTHIOPHANE (DICETOL)

Antimetabolites have been used for some time in the treatment of malignant disorders. Farber et al. (1) used folic acid antagonists and, since then, a number of antimetabolites of purines and pyrimidines have been investigated. One of the important drawbacks of all such compounds is their toxicity to host cells due to non-specicity of action. An ideal drug, therefore, would be one which would have a preferential action on tumour cells. This would be possible if tumour cells were shown to have a distinct biochemical pattern different from that of the host cells. Gadekar and Sahasrabudhe (2) have put forward evidence that there is a relative preponderence of the hexose monophosphate (HMP) pathway activity in neoplastic tissue. On the basis of this suggestion, Sahasrabudhe et al. (3) have reported 2, 5-dicarbethoxy, 3, 4-dihydroxythiophane (dicetol) to be effective in blocking the HMP pathway preferentially in tumour tissue. They have also reported anticancer properties for this compound in transplanted fibrosarcoma in Swiss mice (2-4). Since the compound showed promising results in experimental cancer, it was decided to investigate some of its pharmacological actions. Dicetol was found to produce marked pharmacodynamic effects in experimental animals. Various aspects of this problem are presented in this paper.