TY - JOUR T1 - THE CHEMOTHERAPY OF STREPTOCOCCUS INFECTIONS OF MICE WITH SPECIAL REFERENCE TO SALICYL COMPOUNDS JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 71 LP - 78 VL - 43 IS - 1 AU - JOHN A. KOLMER AU - GEORGE W. RAIZISS AU - ANNA M. RULE Y1 - 1931/09/01 UR - http://jpet.aspetjournals.org/content/43/1/71.abstract N2 - 1. Acridine yellow (No. 1217) gave the highest percentage of survivals (46 per cent) in an amount corresponding to one-fifth of its maximum tolerated dose. This compound however was relatively feeble in bactericidal activity in vitro (1:100). [See table in the PDF file] 2. Next best therapeutic activity was displayed by thymoxyacetic acid (No. 1140) which gave 40 per cent survivals in an amount corresponding to one-fifth of its maximum tolerated dose. This compound was bactericidal in vitro in approximately 1:500 dilution. 3. Compound 546 (3,5-diiodo salicylic acid hexamethyleneamine) and No. 1173 (acriflavine salicylaldehyde) yielded 22 to 23 per cent survivals respectively in amounts varying from one-fourth to one-fifth of their maximum tolerated doses. No. 546 was bactericidal in 1:10,000 in vitro and No. 1173 in a dilution of about 1:1000. [See table in the PDF file] 4. Compound 1108 (mercury thymol azo salicylic acid), compound 1205 (a lead salt of 5-acetyl-amino-salicylic acid) and compound 827 (5 acetyl-amino-acetyl salicylic acid) gave from 10 to 15 per cent survivals in amounts varying from about one-third to one-twentieth of their maximum tolerated doses. These compounds varied in bactericidal activity in vitro from 1:50 (Nos. 827 and 1205) to 1:5000 (No. 1108). 5. With the balance of the new compounds the results were essentially negative in therapeutic activity although it is possible that feeble degrees of therapeutic activity may have been masked by the severity of the experimental infections. 6. Of the 7 control compounds, best results were observed with rivanol which yielded 20 per cent recoveries. This compound was bactericidal in vitro in approximately 1:1000 solution. 7. Neutral acriflavin and gentian violet yielded approximately 10 per cent survivals and in vitro their bactericidal dilutions were approximately 1:1000 for acriflavin and 1:10,000 for gentian violet. 8. Concentrated Pregl's iodine, available for intravenous injection, gave 12.5 per cent survivals in a dose corresponding to 0.6 cc. per kilogram of weight by intraperitoneal injection. Its bactericidal activity in vitro was not determined. 9. Mercurochrome and mercurophen gave essentially negative therapeutic results although it is possible and probable that therapeutic activity on the part of any or all of these substances may have been masked by the severity of the experimental infection as previously stated. Their bactericidal activity in vitro varied from 1:5000 in the case of mercurochrome to 1:200,000 for mercurophen. 10. On the basis of these results it would appear that compounds 1217 (acridine yellow) and 1140 (thymoxy-acetic acid) are especially worthy of clinical trial and one of us (J. A. K.) is now employing them by intravenous injection in dose of 0.005 gram per kilogram (corresponding to 30 cc. of a 1 per cent solution per 60 kgm.) in the treatment of streptococcus septicemia of human beings. ER -