TWO INHIBITORS ACTINC ON A SINGLE ENZYME 



495 



The inhibitions produced on human serum and erythrocyte cholinester- 

 ases by combinations of neostigmine and various tetraalkylammonium salts 

 are very interesting because they illustrate two different types of interaction 

 (Foldes et al, 1960). The results are shown in Table 10-1 and Fig. 10-3. 

 Marked antagonism was demonstrated with the plasma enzyme, which was 

 interpreted as a blocking off of the anionic site from neostigmine by the 

 tetraalkylammonium ions. The lack of antagonism for the erythrocyte 



Table 10-1 

 Multiple Tnhibitiox of Human Cholixesterases " 



" TMA, TEA, TPA, and TBA represent the tetramethyl. -ethyl, -propyl, and -butyl 

 ammonium ions. Xeostigmine was 0.1 n\M for the plasma cholinesterase and 0.2 mM 

 for the erythrocyte cliolinesterase. From Foldes et al. (1960). 



enzyme may be related to the greater negative charge on the anionic site 

 compared to the plasma enzyme, but it could also be explained by differ- 

 ent spatial relations between the anionic and esteratic sites in the two en- 

 zymes. The reaction of acetylcholine with the plasma enzyme anionic site 

 must be interfered with less by the tetraalkylammonium ions than is the 

 case with the erythrocyte enzyme. 



Expression of Multiple Inhibition by Isobols 



Isobols are curves showing equieffective combinations of active substan- 

 ces plotted on graphs whose coordinates are the concentrations of the sub- 

 stances (see Chapter 5). Such curves have been used to demonstrate the 

 nature of the interactions of drug pairs on tissues (Loewe. 1957) but can 

 also be applied to enzyme inhibition. Let us first determine the curves 



