Anti-sulfapyridine and Anti-sulfathiazole Effect of Local Anaesthetics Derived from p-Aminobenzoic Acid

Studies Pertaining to the Antibacterial Activity of Sulfathiazole and its Methyl Derivative

“…That this remarkable inhibitory effect of the drugs was bacteriostatic in nature rather than bactericidal was revealed by successful subculture from those tubes showing no visual evidence of growth. A few workers in this field (Woods 1940, Kahmanson 1940, Keltch et al 1941, and Spink and Jermsta 1941 have employed media of known chemical composition but in no case has any direct comparison been offered between results obtained in synthetic and non-synthetic media.…”

The Mode of Action of Sulfonamides *

“…Much of the responsibility for this extreme variability in the ratio probably lies in the variable amounts of sulfonamide-antagonists already present in practically all culture media. The other sulfonamides under the same experimental conditions require relatively more PABA to counteract their action (70,75,84,115,205,246,281,284,287). Analysis of the quantitative data shows that the potency of each sulfonamide is directly proportional to its ability to counteract the anti-bacteriostatic action of PABA, in other words, the amount of PABA required to counteract bacteriostasis is approximately the same for the minimal bacteriostatic concentration of each sulfonamide (75,128,281,284).…”

The Mode of Action of the Sulfonamides

“…Much of the responsibility for this extreme variability in the ratio probably lies in the variable amounts of sulfonamide-antagonists already present in practically all culture media. The other sulfonamides under the same experimental conditions require relatively more PABA to counteract their action (70,75,84,115,205,246,281,284,287). Analysis of the quantitative data shows that the potency of each sulfonamide is directly proportional to its ability to counteract the anti-bacteriostatic action of PABA, in other words, the amount of PABA required to counteract bacteriostasis is approximately the same for the minimal bacteriostatic concentration of each sulfonamide (75,128,281,284).…”

“…Similarly p-nitrobenzoic acid, p-hydroxylaminobenzoic acid, p-aminobenzamide, p-aminobenzaldehyde, and p-nitrobenzaldehyde may owe their antagonistic action to their conversion to PABA (196,218,227,228,284). Not only procaine, but other local anesthetics derived from PABA counteract sulfonamide action in vivo and in vitro, whereas others not derived from PABA are devoid of activity (115), and as Krahl points out (130) it would be very difficult to prove or disprove that the PABA derivatives owe their activity to hydrolysis to PABA. Johnson et al (107) obtained evidence indicating that the inhibitory action of procaine on bacterial luminescence is not due to its hydrolvsis to PABA; inhibition by procaine was counteracted by increased pressure, whereas pressure had little or no effect on the inhibition caused by PABA.…”