254 



DESCRIPTIONS OF ANTIBIOTICS 



than the d-forin against E. coli in a synthetic 

 medium. The 1-form is inactive unless employed 

 in an asparagine-containing medium, in which it 

 is as active as the d-form (27). d-Cyclo.serine is 

 more active against tuberculosis in mice than the 

 dl- or 1 -forms (29). 



Toxicity: LDso (mice) 1.81 to 2.5 gm per kg 

 intravenously, 2.87 to 4.3 gm per kg, intraperi- 

 toneally, 2.8 to >5 gm per kg subcutaneously, 

 and 5.29 ± 0.20 gm per kg orally. LDso (rat) >5.0 

 gm per kg subcutaneously and orally (18, 19). 

 Rats and mice show slight depression at 0.25 

 gm per kg orally; transient coma at 1 gm per 

 kg, and deep coma at 4 gm per kg. Four gm per kg 

 induce convulsive seizures in rabV)its (17). Four 

 hundred mg per kg per day are severely neurotoxic 

 to monkeys (31). Side reactions in human pa- 

 tients include lethargy, convulsions, and disori- 

 entation (13). Pyridoxine administered simulta- 

 neously is said to reduce the toxicity of cycloserine 

 (40). 



Utilization: Used in tuberculosis as a last resort 

 in combination with other drugs (12, 34). Used for 

 certain other ])acterial infections (11, 24) and 

 leprosy (38). 



References: 



1. Kurosawa, H. J. Antibiotics (Japan) 4: 



183-193, 1951. 



2. British Patent 715,362, September 15, 1954. 



3. Harris, D. A. et al. Antibiotics & Chemo- 



therapy 5: 183-190, 1955. 



4. Cuckler, A. C. et al. Antibiotics & Chemo- 



therapy 5: 191-197, 1955. 



5. Harned, R. L. et al. Antibiotics & Chemo- 



therapy 5: 204-205, 1955. 



6. Shull, G. M. and Sardinas, J. L. Anti- 



biotics & Chemotherapy 5: 398-399, 

 1955. 



7. Sutton, W. B. and Sanfield, L. Antibiotics 



& Chemotherapy 5: 582-584, 1955. 



8. Kuehl, F. A., Jr. et al. J. Am. Chem. Soc. 



77: 2344-2345, 1955. 



9. Hidy, P. H. et al. J. Am. Chem. Soc. 77: 



2345-2346, 1955. 



10. Stammer, C. H. et al . J. Am. Chem. Soc. 



77: 2346-2347, 1955. 



11. Welch, H. p/ «/. Antibiotic Med. 1:72-79, 



1955. 



12. Epstein, I. C. et al. Antibiotic .Med. I: 



80-93, 1955. 



13. Robinson, H. J. et al. Antibiotic Med. 1: 



351-357, 1955. 



14. Barclay, W. R. and Russe, H. Am. Rev. 



Tu be r c . 72 : 236-24 1 , 1 955 . 



15. Steenkon, W., Jr. and Wolinsky, E. Am. 



Rev. Tuberc. 73: 539-546, 1956. 



16. Conzelman, G. M., Jr. and Jones, R. K. 



Am. Rev. Tuberc. 74: 802-806, 1956. 



17. Robinson, H. J. et al. Am. Rev. Tuberc. 



74: 972-976, 1956. 



18. Anderson, R. C. et al. Antibiotics & 



Chemotherapy 6: 360-368, 1956. 



19. Spencer, J. N. and Payne, H. G. Antibiot- 



ics & Chemotherapy 6: 708-717, 1956. 



20. Shoji, J. J. Antibiotics (Japan) 9A: 164- 



167, 1956. 



21. Shibata, M. et al. Ann. Rept. Takeda Re- 



search Lab. 15: 28-35, 1956. 



22. British Patent 757,089, September 12, 1956. 



23. British Patent 758,500, October 3, 1956. 



24. Lillick, L. et al . Antil)iotics Ann. 158- 



164, 1955-1956. 



25. Nakamura, M. Experientia 13:29,1957. 



26. Trivellato, E. and Concilio, C. Giorn. ital. 



chemioterap. 4: 495 498, 1957. 



27. Trivellato, E. Giorn. ital. chemioterap. 



4: 499-503, 1957. 



28. Aburaya, I. and Sugai, T. Chemotherapy 



(Tokyo) 5: 3, 1957. 



29. Serembe, M. and Ziliotto, C!. Minn. Med. 



48: 4212-4224, 1957. 



30. Plattner, P. A. et al. Helv. Chim. Acta 



40: 1531-1552, 1947. 



31. Storey, P. B. and McLean, R. L. Am. Rev. 



Tuberc. 75: 514-516, 1957. 



32. Trivellato, E. and Concilio, C. Bull. soc. 



ital. biol. sper. 33: 463, 1957. 



33. Chang, Y. T. Intern. J. Leprosy 25: 257- 



261, 1957. 



34. Storey, P. B. and McLean, R. L. Anti- 



biotic Med. 4: 223-231, 1957. 



35. British Patent 768,(X)7, February 13, 1957. 



36. Harned, R. L. U. S. Patent 2,789,983, 



April 23, 1957. 



37. Sanford, J. P. e/ «/. Antibiotics Ann. 22-26, 



1957-1958. 



38. Tran-van-Bang. Bull. mem. soc. med. hop. 



Paris 74: 256-258, 1958. 



39. Andrejew, A. et al. Biochim. et Biophys. 



Acta 30: 102-111, 1958. 



40. Epstein, I. G. et al. Antibiotics Ann. 472- 



481, 1958-1959. 



41. Kurihara, T. and Chiba, K. Ann. Rept. 



Tohoku Coll. Pharm. 3: 83-89, 1956. 



42. Freerksen, E. et al. Antibiotica et Chemo- 



ther a pi a 6: 303-396, 1959. 



Oenietliyl tetracyclines 



Produced bji: Streptouu/ces aiireofaciens (mutant 

 of the original Duggar chlortetracycline-pro- 

 ducer). I is produced in chloride-free media; II 

 in chloride-containing media (1). 



