CHEMOTHERAPY 145 



about ten times as soluble as sulpliacliazine at j.>H 7 and 



37 °C. and, although it has about twice the toxicity, it 



would probably be of greater use in the tropics. To take 



another example sulphamerazine, sulphamethyldiazine, 



N— CH 



/ \ ^ % 



NHg/ ^SOa.NH— G CH, IS as active as 



X = C.CH, 

 sulphadiazine, but is less readily eliminated from the 

 body so that an adequate concentration in the blood 

 could be obtained by less frequent administration. 



It has been claimed that the bacteriostatic power of 

 sulphonamides can be reversed by adenine, and by 

 methionine. Adenine sulphate, when administered to 

 mice infected with &ir. j)yogenes in a dose of 0-8 mg. 

 per gram prevents the chemotherapeutic effect of 2 mg. 

 per gram of sulphanilamide or of 4 mg. per gram of 

 sulphadiazine, sulphapyridine or sulphathiazole, being 

 more effective than the same amount of ^-aminobenzoic 

 acid. Guanine and uracil had no such anti-sulphonamide 

 action. Adenine is an essential metabolite for strepto- 

 cocci, forming part of the codehydrogenase and co- 

 phosphorylase systems, and it is considered that the 

 sulphonamides may interfere with these enzjone systems. 

 Methionine, CH3.S.CH2.CH2.CH.NH2.COOH, inhibits the 

 effect of sulphadiazine on E. coli in synthetic medium. 

 This property of methionine is eliminated by urea which 

 also reverses the effect of p-aminobenzoic acid on sul- 

 phanilamide, and increases the potency of sulphadiazine 

 and sulphanilamide, possiblv bv increasing the penetration 



of the drugs into the tissues. Guanidine, ^C=NH, 



and thiourea, ^C=S, are even more active than 



urea. 



