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8-Aminoquinolines

  • Chapter
Antimalarial Chemotherapy

Part of the book series: Infectious Disease ((ID))

Abstract

The 8-aminoquinolines emerged during the 20th century as the only family of antimalarial compounds with activity against multiple life-cycle stages of the plasmodia that infect humans. Primaquine, the lone representative of 8-aminoquinolines among licensed antimalarials, has been in use for over 50 yr. It remains the only drug licensed for the prevention of malaria relapse (i.e., killing liver stages of the parasite). Primaquine also kills asexual blood stages and sterilizes the sexual-stage gametocytes. Thus, primaquine can prevent infection or relapse, cure disease, and prevent transmission of the infection. This broad range of activities represents the promise held in this family of compounds. A new 8-aminoquinoline, tafenoquine (WR 238605), is now in clinical trials and may revolutionize the prevention of malaria in travelers. Moreover, tafenoquine may provide an urgently needed weapon to combat epidemic malaria with a single regimen of therapy. The factor that most jeopardizes such utility is another trait shared by many 8-aminoquinolines, hemolytic toxicity in people lacking glucose-6-phosphate dehydrogenase (G6PD). G6PD deficiency is one of the most common genetic abnormalities in human beings, and it is especially common where malaria is or has been endemic. The challenge for pharmacologists, biochemists, and parasitologists is separating the therapeutic properties of 8-aminoquinolines from hemolytic toxicity. This chapter will summarize knowledge regarding mechanisms of therapeutic and toxic activities and point out areas where further investigation may lead to advances in our understanding of these mechanisms.

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Authors
  1. Ralf P. Brueckner
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  2. Colin Ohrt
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  4. Wilbur K. Milhous
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  1. School of Medicine, University of California, San Francisco, CA, USA

    Philip J. Rosenthal MD

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Brueckner, R.P., Ohrt, C., Baird, J.K., Milhous, W.K. (2001). 8-Aminoquinolines. In: Rosenthal, P.J. (eds) Antimalarial Chemotherapy. Infectious Disease. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-111-4_7

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