A physiological role for the prostaglandins in parturition whereby these substances cause the uterus to contract by enhancing the myometrial response to circulating endogenous oxytocin can at present be only an interesting hypothesis, but the recent development of accurate methods of measuring plasma oxytocin and prostaglandin during labour may allow it to be tested soon.Encouraging results have been obtained with the potentiation of the uterine response exhibited when oxytocin and prostaglandin F2ca or prostaglandin E2 are administered simultaneously. This technique enables the prostaglandin to be infused at one-fifth the usual abortifacient dose and virtually eliminates gastrointestinal side effects. The preliminary work suggests that the abortifacient efficiency of this combinaton is high, probably because the prostaglandin enables the oxytocin to exert its very specific stimulatory action on the myometrium in an efficient manner. A more detailed study of the use of the potentiation of oxytocin and prostaglandin effects to produce mid-trimester abortion is underway.

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N-Acetyl-2,6-dimethyl-p-benzoquinone imine and N-acetyl-3,5-dimethyl-p-benzoquinone imine were prepared from 2,6-dimethylacetaminophen and 3,5-dimethylacetaminophen by oxidation with lead tetraacetate. Reaction of N-acetyl-2,6-dimethyl-p-benzoquinone imine with hydrochloric acid gave 3'-chloro-2',6'-dimethyl-4'-hydroxyacetanilide, whereas ethanethiol, aniline, and ethanol gave tetrahedral adducts resulting from addition to the imine carbon. Water gave 2,6-dimethyl-p-benzoquinone. With N-acetyl-3,5-dimethyl-p-benzoquinone imine, water and aniline gave substitution on the imine carbon, yielding 2,6-dimethyl-p-benzoquinone and 3,5-dimethyl-N-phenyl-p-benzoquinone imine, respectively. Ethanethiol gave 3'.5'-dimethyl-2'-(ethylthio)-4'-hydroxyacetanilide. The toxicity of 2,6-dimethylacetaminophen and 3,5-dimethylacetaminophen was examined histologically in mice and rats. 3,5-Dimethylacetaminophen was slightly more nephrotoxic but showed a similar hepatotoxicity to acetaminophen. 2,6-Dimethylacetaminophen, like N-methylacetaminophen, showed very little tissue damage.

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SummaryBoth aspirin and phenacetin derivatives were shown to be nephrotoxic when administered to rats as a single intravenous injection. Phenacetin derivatives tended to produce more severe renal damage and to be nephrotoxic in smaller doses than aspirin derivatives. With the exception of a single derivative, the renal lesions were confined to the proximal convoluted tubule, even after administration of compounds which under other conditions have induced renal papillary necrosis.