VIII. The physiological action of the nitrites of the paraffin series, considered connection with their chemical constitution

Abstract

The present investigation was commenced three years ago, in order to throw further light on the mode of action of the paraffinic nitrites when introduced into the animal organism, and particularly to determine in what manner this action is conditioned by the different chemical constitution of the various nitrites employed. Since the chemical constitution of these compounds is well established and their molecules are comparatively simple in structure, and moreover as their principal physiological effects are capable of accurate quantitative study, it seemed likely that the inquiry would furnish valuable pharmacological results. Although the investigation, both on its chemical and physiological sides, has proved to be far more laborious and difficult than was anticipated, unexpected difficulties having arisen which have rendered necessary the employment of specially-devised apparatus, and the execution of several series of experiments in order to control the accuracy of the results first obtained, yet the conclusions we have finally reached will serve, we think, not only to elucidate the modes of action of these compounds, and to establish the manner of their dependence on the presence of certain groups in the respective molecules, but we hope may also be of some importance in their bearings on the treatment of disease. It is already known that the physiological action of amyl and ethyl nitrites closely resembles in its important features that of the metallic nitrites, and that the characteristic effect is due to the presence in both series of compounds of the nitroxyl group NO 2 , the nitrogen of this group not being directly united to the metal or organic radical, but indirectly by means of an atom of oxygen (R’ONO). Our knowledge of the physiological behaviour of the organic nitrites has been almost wholly derived from the study of amyl nitrite, which has been observed to produce a similar, but far greater, effect than its lower homologue, ethyl nitrite, whose action, however, has not hitherto been so closely examined as that of the amyl compound. Both these organic nitrites are therapeutically employed, the amyl compound at the suggestion of Lauder Brunton , who proposed to use it in the treatment of certain diseases on account of its known physiological action. Unfortunately, however, it seems likely that most of the results which have been obtained with amyl nitrite are to a large extent vitiated by the circumstance that, as a rule, sufficient pains have not been taken to procure the nitrite in a chemically pure state. One of us has already shown that the material usually employed in medicine under the name of amyl nitrite is highly impure, containing a large proportion of other nitrites (ethyl, propyl, butyl), as well as their oxidation products. The redistilled amyl nitrite which has been employed by some investigators is a mixture of two amyl nitrites with a variable proportion of iso-butyl nitrite. In the present investigation special precautions were taken to obtain the various nitrites in a pure state. The compounds selected for examination were: methyl nitrite, ethyl nitrite, primary propyl nitrite, secondary propyl nitrite, primary butyl nitrite, iso-butyl nitrite, secondary butyl nitrite, tertiary butyl nitrite, α -iso-amyl nitrite, β -iso-amyl nitrite, tertiary amyl nitrite. These nitrites were chosen because they contain nitroxyl united to typical and differently constituted radicals. Their examination would, therefore, enable us to determine the modifying influence exerted by these radicals upon the characteristic action of nitroxyl.