FIELDS W, X, and Y 



Columns 68; 69 and 



70; and 71 



As the discussion of Division 16 has indicated, the CBCC has devised no code criterion for 

 data in which antagonism is demonstrated to be of some degree of intensity less than 100% in the 

 individual organism (e. g. , "50% inhibition of the muscle contraction caused by the secondary 

 compound"). At present, this incomplete inhibition can be coded only by evaluating merely on the 

 basis of percentage inhibition (Criterion 62), ignoring the dosage ratio. As has been suggested, in 

 the final paragraphs of Subdivision A in Division 8, a dosage-response intensity correlation might be 

 possible by devising a special grid on which the highest percentage antagonism (in the individual 

 organism) of which the compound is capable is correlated with the minimum dose (an antagonism dose 

 ratio) demonstrated to be capable of causing that degree of antagonism. This would supplement 

 Criterion 22 by providing an expression of relative potency (for antagonism in the individual organism) 

 for each test compound, which Criterion 62 can not provide. 



If data occur in which dosage size and percentage of individuals responding are correlated (as 

 with Criterion 55) but, in addition, the antagonism of the response to the secondary compound is less 

 than 100% in the individual organism, it is suggested that a new criterion be established, bearing in 

 its definition the stipulation that the dosage size and percentage of individuals responding are correlated 

 and that the degree of antagonism in the individual is less than 100% (either ignoring this degree of 

 antagonism in the individual or establishing a special criterion for each standard level such as 50% 

 antagonism, 80% antagonism, etc. ) 



When Criterion 55 is used, antagonism of the secondary compound's action has been demon- 

 strated by the test, otherwise it would be negative data coded by Criterion 01, 02, or 62 with Symbol 1 

 in Field Y and Symbol J or K in Field W. Therefore, when Criterion 55 is used, Field W is coded with 

 Symbol L or M, if only one dose were tested and complete antagonism occurred in less than 100% of the 

 individuals tested. If several tests were run, each at different dosage levels, so that a curve is 

 drawn on the Grid, Field W is coded with Symbol or P, according to whether one of the doses tested 

 produced complete antagonism in 100% of the individuals tested and is the minimum dose needed to 

 cause complete antagonism in 100% of the individuals (Symbol 0) or whether the highest dose adminis- 

 tered did not produce the antagonism in 100% of the individuals tested (Symbol P). If all doses tested 

 cause complete antagonism in all individuals tested (100%) to which those doses are administered, 

 Criterion 55 cannot be used, but only Criterion 62 with Symbol 9 in Field Y and with Symbol N in Field W. 



22. Evaluation of synergism in Fields X and Y 



Synergism, like antagonism, is an effect of one compound (the test compound) on the biological 

 response to another compound (the secondary compound) and it is defined and discussed in the section 

 on Specific Directions and Explanations for Field T- 1 (Division 12). Its occurrence is indicated by 

 code in Field T-l with Symbol 8. 



One distinction between synergism and antagonism is that antagonism has a well-defined 

 limitation of maximum intensity (i. e. , 100% response intensity) beyond which the test compound action 

 can no longer be defined as antagonism, but only as a reversal of the response to the secondary 

 compound. Synergism, on the other hand, is limited only by the individual characteristics of the 

 organism, of the secondary compound, and of the test compound; it can be less than 100% increase of 

 the response to the secondary compound when administered alone, but it can also be more than 100% 

 increase. 



Thus, in the case of synergism, there is no point analogous to the point in antagonism described 

 as "complete" antagonism, except by the limitations on a specific synergistic action imposed by the 

 factors just mentioned as characterizing the specific testing situation. Consequently, in the case of 

 synergism, both of two variables need always to be coded to permit subsequently an evaluation of the 

 test compound's relative potency as a synergist: (1) the degree of synergistic action and (2) the minimum 

 quantity of test compound necessary for that degree of synergism. Note that, when coding antagonism 

 (Criterion 22 or 55), the degree of antagonism is not coded. 



As with Criteria 22 and 55, no standard mechanism has as yet been devised by the CBCC for 

 correlating these two factors to derive a single comparative evaluation figure, though a special grid 

 suggested in the discussion of Criterion 22 (see the second paragraph of Division 21) might be adapt- 

 able to synergism data. 



203 - 



