NEW DRUGS ACHIEVE IMPORTANT RESULTS

Press, Volume LXXIX, Issue 24022, 10 August 1943, Page 4

NEW DRUGS ACHIEVE IMPORTANT RESULTS

THE SULPHONAMIDES

On Christmas Day, 1932, a German patent No. 607537 was granted for a dye named prontosil which appeared to have remarkable properties in protecting against bacterial infection. Thus began the fascinating story of the large family of drugs of the sulphonamide group which have revolutionised the treatment of many acute infections. Indeed, the director of the laboratory m which the early experiments were made considered the results so fantast c that he delayed publication for nearly three years, so that false hopes might not be raised. Actually the drug or rather the dye had been known since 1908. In the same year workers m France were claiming good results witn something similar; and the power .of certain dyes to deal with disease was being closely studied in the years before the last war. But the real story begins with prontosil. the value of which was shown oy carefully planned trials in this country. At Queen Charlotte’s Hospital in London a campaign against maternal mortality was in progress. When prontosil became available its effects were tried on the dreaded puerperal (or childbed) fever caused by a particular variety of microbe known as the haemolytic streptococcus. Again the results were almost too good to be true and the research workers showed the greatest caution before publishing what they had found. Incidentally, the maternal mortality rate has gone down and stayed down from that time onwards. Origin of a Name This brings the story to 1936. The next step was the discovery that it was not the actual dye which was the valuable agent, but a colourless product formed from it in the body. Complicated as nomenclature has become in this story, it is of historical interest to note the full name of this substance, which is the real parent of all the later developments. It is termed paraaminobenzenesulphonamide; and the term sulphonamide is now used for the whole group. Immediate trials were made with all sorts of bacterial infections. It was found that the original drug, called sulphanilamide, was limited in its scope. Other infections caused by the haemolytic streptococcus were treated with success, notably erysipelas, and so were one or two other types of infection; but there was no effect on many serious maladies. Then began a great period of chemical research, during which many minor variations of the original drug were marketed and a whole host of derivatives patiently prepared and tested. In 1938 came the next important step, when the preparation numbered 693 in a certain laboratory was found to be effective against the bacteria causing pneumonia. This is now known as sulphapyridine; and the first clinical trials in this country showed a reduction of over two-thirds in the mortality from pneumonia. Moreover, it was found that this drug had a wider range of activity than the original sulphanilamide. Meningitis came into the list of diseases which could sometimes be cured with it. Still the search went on; and next came a variation dealing with the staphylococcal microbe—the cause of infection in skin and bone disorders. This was called sulphathiazole. With these three main preparations an attack upon most of the acute infections of the body was now possible. But as the chemists were not satisfied, the last few years have seen still more developments. For dysentery there is now sulphaguanidine, and for certain local uses, as for example in the eye, sulphacetamide. Certain disagreeable effects of the drugs continued to give trouble. Research has brought sulphathiazine from America and sulphamethazine from this country as modern varieties which apparently do all that the origi-

(By the Medical Correspondent of “The Times.") (Published by Arrangement.)

nal drugs will do but more plea«m*v and with less risk. v asa % For it must be realised that tho« powerful chemicals do not always fine their activities to the bacteria nl disease. Although the risk is relative!* small—recent American figures that one death occurs from the sul phonamide drugs in every 2571 death* from all causes—it is certainly then* none of the sulphonamides should used except under the closest super vision. Toxic effects upon the -blood' the skin, the nervous system, an htW systems have all been reported.voftS . increasing experience 'V '> creased danger; modern preparatidu are probably much safer than thS prototypes. Ways and Means Given usually by the mouth in th» familiar bulky tablets, the sulphonamides are sometimes used in other ways. Certain preparations can be in. jected, and in powdered form they have ' been used for war wounds, for disinfecting operation sites, and even as a form of nasal snuff. Recent reports have suggested that a form of the dnu , might be used as chewing gu m for* some affections of the mouth and throat; and eye drops have already re. ■ volutionised the treatment of some types of industrial eye injury. The mode of action of the sulphonamides is still not altogether certain They do not directly kill bacteria, as disinfectants do, nor neutralise the pop sons produced by bacteria. It is thought they somehow interfere with the bac. terlal chemistry, preventing (he germs from getting essential foodstuff because they themselves closely resemble that foodstuff. It is as if a vitamin essential for life were kept from getting: into the bacterial cell because the sul--phonamide had already filled the gap. This process of “interference by inhibp tion” is of importance because itmeans that a knowledge of bacterial chemistry and feeding habits may point the'/ way to the further preparation oh drugs capable of wrecking some essen-, ' tial process upon which bacterial life : depends. Gaps to be Filled This may lead to great developments in the future, for there are still gaps where those sulphonamides at present available fail lamentably. The whol*» group of diseases due to viruses, ttm which true Influenza is one, are not f ’ fundamentally influenced, although 4 complications due to other bacterial may be attacked. Nor as yet has any | sulphonamide been found which' wiUj deal with the. bacillus causing tubercu-1 losis. , ;; , f Many patients all over the world, ? animal as well us human, owe their ! lives to the sulphonamides. The effect I is beginning to show itself in the vital | statistics of the nation. Writing re-| cently of the mortality rates in Eng-1 land and Wales for 1942, the medical ! • statistician in the General Register if Office concluded that “it seems to me j reasonable to conclude from the figures ! that the lives saved by the sulphona-L mides in 1942 ran well into fiver, figures." War surgery has become very I much safer since these drugs were i available. Or- special correspondent in North Africa wre'e recently of nior-; tality statistics that would amaze the ; world. Sensis in that campaign largely controlled by sulphonamide;’ drugs. But it is only fair to add that ; much of the experiment:,! work hat'; necessitated animal experiments, and [, scientists all over the world get not a’ little impatient when subjected to the criticism of those mistaken enough to object to this essential type of research. * Never in so short a space of time'nM such a revolution been wrought hype treatment of So many though other weapons mus, used in conjunction with the mides, there is no therapeutic day with a popularity so and so worthily attained."