CHEMOTHERAPY 135 



due to Ehrlich who suggested that the drugs were taken 

 up by specific chemoreceptors attached to susceptible 

 organisms, but lacking in cells not affected by the drug. 

 The subsequent action of the drugs was not described 

 except that they were considered not to kill the micro- 

 organism but to prevent multiplication, enabling the 

 host to deal effectively by its normal processes with the 

 consequently milder infection. 



Later, when the importance of enzymatic processes 

 in metabolism began to be realised, suggestions were put 

 forward that drugs in general might act by inhibiting 

 enzyme systems and so upsetting the normal course of 

 events in the animal body. A number of such effects 

 had been observed in vitro ; cyanides inhibit oxidases, 

 atoxyl and quinine inhibit lipases, cocaine, atropine and 

 pilocarpine inhibit yeast invertase, eserine inhibits the 

 break down of acetylcholine by esterase, acriflavine 

 inhibits a hydrogen transportase system in trypanosomes, 

 which is not affected by cyanide. 



Another type of enzyme inhibition is that due to the 

 presence of excess of the products of the reaction or of 

 substances having a constitution similar to the substrate 

 or to the products of breakdowTi. For example, the 

 breakdown of lactic acid, CH3CHOH.COOH, to pyruvic 

 acid, CH3CO.COOH is partially inhibited by a-hy- 

 droxybutyric acid, C2H5CHOH.COOH, glyceric acid, 



CH2OH.CHOH.COOH, mandelic acid, (^ ^CHOH.COOH, 



glyoxylic acid, HCO.COOH, or oxalic acid7H0.C0.C00H. 

 The action of succinic dehydrogenase in converting 

 succinic acid, COOH.CH2.CH2.COOH, to fumaric acid, 

 COOH.CH=CH.COOH, is inhibited by the presence 

 of malonic acid, COOH.CHg.COOH or glutaric acid, 

 COOH.CH2.CH2.CH2.COOH, containing the -CHgCOOH 

 group (see p. 190). The heavy metals such as mercury 

 and barium also have an inliibitory effect on many 



