p-AMINOBENZOIC ACID 487 



acts the therapeutic effect of locally applied sulfathiazole against gas- 

 gangrene, 60 and antagonizes the action of sulfanilamide on pneumococci 

 in vivo as well as in vitro.™ 



From the in vitro activity of procaine for Streptococcus hemolyticus 1 

 (Table 2) it has been calculated that the average amount of procaine 

 used in minor surgery should be sufficient to inhibit all the sulfanilamide 

 in the human body, even during intensive treatment. 53 ' 58 The concentra- 

 tion in the pleural fluid of patients under procaine anesthesia has been 

 reported to be 0.0002 per cent, which is sufficient to prevent completely 

 the bacteriostasis resulting from 0.05 per cent sulfapyridine for Pneumo- 

 coccus III (T 3-1) in vitro. 48 



However, procaine and its metabolic products are rapidly excreted 

 within 10 to 12 hours by the rabbit, 52 and presumably by other organisms. 

 This tends to minimize the deleterious effect of such anesthetics on the 

 chemotherapeutic action of sulfonamides. Three clinical cases, one strep- 

 tococcal infection treated with sulfanilamide and one streptococcal and 

 one pneumococcal infection on sulfapyridine therapy, have been pre- 

 sented in which procaine was used as a local anesthetic without more 

 than transient ill effect on therapy. 53 However, the use of local anesthetics 

 derived from p-aminobenzoic acid is contraindicated during sulfonamide 

 therapy. 



Since /?-dimethylaminoethyl p-n-butylaminobenzoate (Table 2) is rela- 

 tively inactive in preventing sulfonamide bacteriostasis, a group of esters 

 and amides of p-alkylaminobenzoic acids have been prepared as possible 

 local anesthetics with diminished ability to prevent sulfonamide bac- 

 teriostasis. These compounds in general were ineffective in preventing 

 sulfonamide bacteriostasis for Escherichia coli and Streptococcus hemo- 

 lyticus? - 56 > 57 



N-(p-Aminobenzoyl)-L-glutamic Acid. The first indication of the in- 

 volvement of glutamic acid in the metabolism of p-aminobenzoic acid 

 was the report of Auhagen, 05 who found that N- (p-aminobenzoyl) -l- 

 glutamic acid is eight to ten times as effective as p-aminobenzoic acid in 

 preventing the toxicity of sulfanilamide for Streptobacterium plantarum 

 10 S. 



H 2 N— / \— CO— NH— CH— CH 2 — CH 2 — COOH 

 \=S COOH 



N-{p-aminobenzoyl)-i^-glutamic acid 



The corresponding p-aminobenzoyl derivatives of D-glutamic acid, 

 L-aspartic acid, d- or L-leucine, glycine or glycylglycine were compara- 



