The Natural Penicillins — Benzylpenicillin (Penicillin G) and Phenoxymethylpenicillin (Penicillin V)

  • A. P. Ball
  • J. A. Gray
  • J. McM. Murdoch


The two so-called natural penicillins are both produced biosynthetically from Penicillium chrysogenum by fermentation. Benzylpenicillin (penicillin G) is formed if phenylacetic acid is added to the culture medium and Phenoxymethylpenicillin (penicillin V) is formed when phenoxyacetic acid is added. Deacylation of penicillin G is brought about by amidase enzymes of bacterial origin which split off the side chain leaving the ‘penicillin nucleus’ or 6-aminopenicillanic acid (6-APA). The ‘new’ or semi-synthetic penicillins (section 4) are derived by grafting different side chains onto 6-APA so conferring widely differing pharmacological and antibacterial properties. The 6-APA nucleus itself consists of a thiazolidine ring fused to a β-lactam ring. This structure is converted into bacteriologically inert penicilloic acid by the enzyme β-lactamase or penicillinase which splits open the β-lactam ring (fig. 1). Some of the semisynthetic penicillins possess bulky side chains which by stearic hindrance mechanisms protect the β-lactam ring from penicillinase; both of the natural penicillins and semisynthetic penicillins such as ampicillin which possess less heavy side chains, remain entirely vulnerable to penicillinase action.


Penicillin Versus Phenoxyacetic Acid Benzathine Penicillin Procaine Penicillin Semisynthetic Penicillin 
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  1. Ashford, W.A.; Golash, R.G. and Hemming, V.G.: Penicillinase-producing Neisseria gonorrhoeae. Lancet 2: 657–658 (1976).PubMedCrossRefGoogle Scholar
  2. Baldwin, D.S.; Levine, B.B.; McCluskey, R.T. and Gallo, G.R.: Renal failure and interstitial nephritis due to penicillin and methicillin. New England Journal of Medicine 279: 1245–1252 (1968).PubMedCrossRefGoogle Scholar
  3. Barber, M. and Rozwadowska-Dowzenko, M.: Infection by penicillin-resistant staphylococci. Lancet 2: 641–644(1948).PubMedCrossRefGoogle Scholar
  4. Barber, M.: Coagulase-positive staphylococci resistant to penicillin. Journal of Pathology and Bacteriology 59: 373–384(1947).CrossRefGoogle Scholar
  5. Brunner, F.P. and Frick, P.G.: Hypokalaemia, metabolic alkalosis and hypernatraemia due to ‘massive’ sodium penicillin therapy. British Medical Journal 4: 550–552 (1968).PubMedCrossRefGoogle Scholar
  6. Contoyiannis, P. and Adamopoulos, D.A.: Penicillin-resistant Neisseria meningitidis. Lancet 1: 462 (1974).PubMedCrossRefGoogle Scholar
  7. Crofton, J.W.: Some principles in the chemotherapy of bacterial infections. British Medical Journal 2: 137–141 (1969).PubMedCrossRefGoogle Scholar
  8. Ettinger, E. and Kaye, D.: Systemic manifestations after a skin test with penicilloyl-polylysine. New England Journal of Medicine 271: 1105–1106 (1964).PubMedCrossRefGoogle Scholar
  9. Fishman, L.S. and Hewitt, W.L.: The Natural Penicillins. Medical Clinics of North America 54: 1081–1099(1970).PubMedGoogle Scholar
  10. Fishman, R.A.: Active transport and the blood-brain barrier to penicillin and related organic acids. Transactions of the American Neurological Association 89: 51–55 (1964).PubMedGoogle Scholar
  11. Fishman, R.A.: Blood-brain and CSF barriers to penicillin and related organic acids. Archives of Neurology 15: 113–124(1966).PubMedCrossRefGoogle Scholar
  12. Garrod, L.P., Lambert, H.P. and O’Grady, F.: Penicillins 1. Natural; in Antibiotic and Chemotherapy, 4th ed, p.53, 55 (Churchill Livingstone, Edinburgh and London 1973).Google Scholar
  13. Gilbert, D.N.; Gourley, R.; d’Agostino, A.; Goodnight, S.H. and Worthen, H.: Interstitial nephritis due to methicillin, penicillin and ampicillin. Annals of Allergy 28: 378–385 (1970).PubMedGoogle Scholar
  14. Goslings, W.R.O.: Introductory remarks in Advances in Penicillin Allergy and Immunology, Proceedings of the Symposium, Rotterdam, p.8 (Beecham Research Laboratories, 1970).Google Scholar
  15. Hamilton-Miller, J.T.: Inhibition of β-lactamase: a continuing story. Journal of Antimicrobial Chemotherapy 3: 195–196(1977).PubMedCrossRefGoogle Scholar
  16. Hansman, D., Glasgow, H.; Sturt, J.; Devitt, L. and Douglas, R.: Increased resistance to penicillin of pneumococci isolated from man. New England Journal of Medicine 284: 175–177 (1971).PubMedCrossRefGoogle Scholar
  17. Kunin, C.M.: Clinical significance of protein binding of the penicillins. Annals of the New York Academy of Sciences 145: 282–289 (1967).PubMedCrossRefGoogle Scholar
  18. Leading Article: Penicillins and nephropathy. Lancet 2: 447 (1974).Google Scholar
  19. Leading Article: Penicillinase-producing gonococci. Lancet 2: 725–726 (1976).Google Scholar
  20. Leading Article: Immunological tolerance to treat penicillin allergy? Lancet 2: 943 (1976).Google Scholar
  21. Lerner, P.I.; Smith, H. and Weinstein, L.: Penicillin neurotoxicity. Annals of the New York Academy of Sciences 145: 310–317(1967).PubMedCrossRefGoogle Scholar
  22. Levine, B.B. and Zolov, D.M.: Prediction of penicillin allergy by immunological testing. Journal of Allergy 43: 231–244(1969).PubMedCrossRefGoogle Scholar
  23. Lynn, B.: The Semi-synthetic Penicillins; in Antibiotica et Chemotherapia, Vol. 13, p. 131 (S. Karger, Basle and New York 1965).Google Scholar
  24. Morrison, A.W.: Phenethicillin and benzylpenicillin in acute otitis media. British Medical Journal 2: 8–11 (1961).PubMedCrossRefGoogle Scholar
  25. Munro, A.C.: Immunology of macro molecular residues in penicillins; in Advances in Penicillin Allergy and Immunology, Proceedings of the Symposium in Rotterdam, p.67–77 (Beecham Research Laboratories 1970).Google Scholar
  26. Orchard, R.T. and Rooker, G.: Penicillin-hypersensitivity-nephritis. Lancet 1: 689 (1974).PubMedCrossRefGoogle Scholar
  27. Park, J.T. and Strominger, J.L.: Mode of action of penicillin: Biochemical basis for the mechanism of action of penicillin and for its selective toxicity. Science 125: 99–101 (1957).PubMedCrossRefGoogle Scholar
  28. Petz, L.D. and Fudenberg, H.H.: Coombs-positive hemolytic anaemia caused by penicillin administration. New England Journal of Medicine 274: 171–178 (1966).PubMedCrossRefGoogle Scholar
  29. Phillips, I.: β-lactamase-producing, penicillin-resistant gonococcus. Lancet 2: 656–657 (1976).PubMedCrossRefGoogle Scholar
  30. Rolinson, G.N.: The significance of protein binding of penicillins; in Brumfitt and Williams Therapy with the New Penicillins, p.20 (Fellowship of Post Graduate Medicine, London 1964).Google Scholar
  31. Shaltiel, S.; Mizrahi, R. and Sela, M.: On the immunological properties of penicillins. Proceedings of the Royal Society of London 179: 411–432 (1971).PubMedCrossRefGoogle Scholar
  32. Smith, H.: in Antibiotics in Clinical Practice, p.208 (Pitman Medical, London 1972).Google Scholar
  33. Spratt, B.G.: The action of mecillinam. Journal of Antimicrobial Chemotherapy 3 (Suppl. B): 13–19 (1977).PubMedGoogle Scholar
  34. White, J.M.; Brown, D.L.; Hepner, G.W. and Worlledge, S.M.: Penicillin-induced haemolytic anaemia. British Medical Journal 3: 26–29 (1968).PubMedCrossRefGoogle Scholar

Copyright information

© ADIS Press 1978

Authors and Affiliations

  • A. P. Ball
    • 1
  • J. A. Gray
    • 2
  • J. McM. Murdoch
    • 2
  1. 1.Department of Medicine (Sub-department of Communicable and Tropical Diseases)The University of BirminghamEngland
  2. 2.Infectious Diseases UnitCity HospitalEdinburghScotland

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