Abstract

1. Injection of suitable single doses of sodium nostal (Na isopropyl betabromallyl barbituric acid) very readily caused delayed or secondary death in the rat, usually in one to four days, and accompanied by fatty changes in the liver, kidney, heart and lungs, and by edema of the lungs, usually with pneumonia. Even subhypnotic doses may cause delayed death. Both hematoxylin and eosin and also a fat stain, such as scarlet red, are needed to show the total pathological changes.

2. The close chemical relative, pernoston (Na 2-butyl betabromallyl barbiturate) also caused such delayed death and pathological changes, but only after relatively large doses. Administering a small dose at 2-week intervals for 28 weeks neither caused delayed death, nor fatty changes in the liver.

3. Further lengthening of the carbon chain, as in rectidon (Na 2-amyl betabromallyl barbiturate), or methylation of one nitrogen in nostal, as in eunarcon, shortened the hypnotic action markedly, and delayed death became very exceptional after doses which killed some rats acutely. In case of pernoston, rectidon and eunarcon there was also a marked sex-difference in the rat, which has previously been described for the first named.

4. The chlorine homologue of nostal caused delayed death in the rat nearly as readily as did nostal, the dichlor-allyl barbiturate appeared a little weaker in this respect, and no such death occurred after administration of the chlorine homologue of pernoston.

5. Sodium alurate, the hydrogen homologue of nostal, did not cause delayed death in rats when given alone, with pilocarpine, with sodium bromide or with hydrobromic acid, the former indicating that increased salivary and mucous secretion is not the important factor, and the latter that neither the bromide ion, nor the acid liberation were the important factors. This latter was further confirmed, because increasing the alkali reserve by adding sodium bicarbonate or sodium citrate to the diet failed to prevent delayed death.

6. Following administration of the related diallyl, isopropyl ethyl (ipral), or acetonyl isopropyl barbiturate, one of the nostal decomposition products, or ten other barbiturates of varying type, using about 500 rats, delayed death occurred but once in a severe evipal poisoning.

7. Experiments upon a few rabbits indicated that this animal is more resistant to nostal than is the rat, and tests upon 30 mice demonstrated that these rodents are very resistant; no delayed death occurred even when they had been severely poisoned with nostal.

8. Although the clinical literature indicates that the resistance of man to nostal and pernoston is very high, the delayed deaths and the very definite pathological changes in the vital organs of the rat following administration of these drugs would seem to make a restudy of their action upon man and other resistant mammals highly desirable.