The Convulsive Action of 2,5-Dicarbethoxy 3,4-Dihydroxythiophane (Dicetol)

Abstract

Antimetabolites have been used for some time in the treatment of malignant disorders. 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 inves tigate some of its pharmacological actions.Dicetol was found to produce marked pharmacodynamic effects in experimental ani mals. Various aspects of this problem are presented in this paper. MATERIALS AND METHODSAll experiments were carried out with mice (Swiss strain), rats (Wistar strain) and cats. Dicetol in N/250 sodium bicarbonate (pH 8) was administered in varying doses intravenously (i.v.) in mice and rats and the effects were noted. The fluid injected did not exceed 0.2 ml. It was previously ascertained that the same volume of the solvent did not produce any effects in mice. On the basis of the effect seen, the dose causing convulsions in 50% of the animals (CD,,) was calculated by the method of Litchfield and \Vilcoxon (5). The effects of dicetol on pentobarbital and ether induced sleeping time were also noted. Dicetol was injected in varying doses, i.v., followed 30 minutes later by pentobarbital sodium, 50 mg/kg, intraperitoneally (i.p.). In the ether hypnosis experiments, dicetol was injected i.v. in a dose of 40 mg/kg and 30 minutes later, the animals were placed individually under a beaker of 500 ml capacity and exposed for 2 minutes to 2 ml of ether.Since dicetol caused convulsions in mice, the effect of reserpine on dicetol induced convulsions was also studied. Reserpine was administered in a dose of 2.5 mg/kg i.p. for two consecutive days and dicetol injected 24 hours after the last dose of reserpine.