Leishmaniasis pp 441-448 | Cite as

The Role of Membrane-Stabilizing Drugs on Uptake of Leishmania Parasites by Human Macrophages

  • A. Kharazmi
  • A. L. Sørensen
  • H. Nielsen
Part of the NATO ASI Series book series (NSSA, volume 171)


More than 12 million people are infected with different species of Leishmania and the annual death toll due to leishmaniasis is over 5000. Treatment of the patients with different forms of leishmaniasis is still a serious problem. Pentavalent antimonials in conventional doses are ineffective against visceral leishmaniasis and at higher doses toxic. The usual second line drugs such as pentamidine and amphotericin B are also toxic and difficult to administer. There is therefore a great need to search for drugs that are safe and can ef¬fectively control the disease.


Visceral Leishmaniasis Trypanosoma Brucei Antileishmanial Activity Lipid Fluidity Leishmania Donovani 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Blackwell JM (1985) Receptors and recognition mechanisms of Leishma¬nia species. Trans. Roy. Soc. Trop. Med. Hyg. 79: 606–612.PubMedCrossRefGoogle Scholar
  2. Chang CS, Chang KP (1986) Monoclonal affinity purification of a leish-mania membrane glycoprotein and its inhibition of leishmania-macro-phage binding. Proc. Nat. Acad. Sci. 83: 100–104.PubMedCrossRefGoogle Scholar
  3. Elias E, Boyer JL (1973) Chlorpromazine and its metabolites alter po-lymerization and gelation of actin. Science. 206: 1404–1406.CrossRefGoogle Scholar
  4. Handman E, Goding JW (1985) The Leishmania receptor for macrophages is a lipid-containing glycoconjugate. EMBO J. 4: 329–336.PubMedGoogle Scholar
  5. Heron DS, Shinitzky M, Hershkowitz M, Samuel D (1980) Lipid fluidity markedly modulates the binding of serotonin to mouse brain membra¬nes. Proc. Nat. Acad. Sci. 77: 7463–7467.PubMedCrossRefGoogle Scholar
  6. Kristiansen JE, Gaarslev K (1985) The antibacterial effect of selected neuroleptics on Vibrio cholerae. Acta Path. Microbiol. Immunol. Scand. Sect. B. 93: 49–51.Google Scholar
  7. Kristiansen JE, Jepsen S (1985) The susceptibility of Plasmodium fal-ciparum in vitro to chlorpromazine and the stereo-isomeric compounds cis(Z)-and trans(E)-clopenthixol. Acta Path. Microbiol. Im-munol. Scand. Sect. B. 93: 249–251.Google Scholar
  8. Lohr KM, Feix JB, Kurth C (1984) Chlorpromazine inhibits neutrophil Chemotaxis beyond the chemotactic receptor-ligand interaction. J. Infect. Dis. 150: 643–652.PubMedCrossRefGoogle Scholar
  9. Ogiso T, Iwaki M, Mori K (1981) Fluidity of human erythrocyte membrane and effect of chlorpromazine on fluidity and phase seperation of membrane. Biochem. Biophys. Acat. 649: 325–335.CrossRefGoogle Scholar
  10. Pearson RD, Manian AA, Harcus Jl, Hall D, Hewlett EL (1982) Lethal effects of phenothiazene neuroleptics on the pathogenic protozoan Leishmania donovani. Science 217: 369–371.PubMedCrossRefGoogle Scholar
  11. Pearson RD, Manian AA, Hall D, Harcus JL, Hewlett EL (1984) Antileishmanial activity of chlorpromazine. Antimicrob. Agents Chemoth. 25: 571–574.CrossRefGoogle Scholar
  12. Pearson RD, Brand JJ, Roberts D, Hewlett EL (1987) Antiprotozoal effects of thioxanthenes against the human pathogen Leishmania donovani. Experientia. In press.Google Scholar
  13. Petersen PV, Nielsen IM, Pedersen V, Jørgensen A, Lassen N (1977) Thioxanthenes in: Psychotherapeutic drugs, ed. E. Udsin & I. Forrest. Marcel Dekker. New York. P. 827–867.Google Scholar
  14. Rechnitzer C., Kristiansen JE, Kharazmi A (1985) In vitro modulation of human neutrophil Chemotaxis by cis(Z) -and trans (E)-clopenthixol and chlorpromazine. Acta Pathol. Micro¬biol. Immunol. Sec. C. 93: 199–203.Google Scholar
  15. Seebeck T, Gehr P (1983). Trypanocidal action of neuroleptic pheno-thiazenes in Trypanosoma brucei. Mol. Biochem. Parasitol. 9: 197–208.PubMedCrossRefGoogle Scholar
  16. Smith RJ, Bowmann BJ, Iden SL (1981). Effects of trifluoperazine on human neutrophil function. Immunol. 44: 677–684.Google Scholar
  17. Suda T, Shimizu D, Maeda N, Shiga T (1981). Decreased viscosity of human erythrocyte suspension induced by chlorpromazine and isoxsusprine. Biochem. Pharmacol. 30: 2057–2064.PubMedCrossRefGoogle Scholar
  18. Trouet A, Tulkens P, Schneider YJ (1980). Subcellular localization of infectious agents: Pharmacological and pharmacokinetic impli¬cations. In: The Host Invader Interplay, ed. Van den Bossche, North Hollan H. p. 31–44.Google Scholar
  19. Zilberstein D, Dwyer DM (1984). Antidepressants cause lethal disrup¬tion of membrane function in the human protozoan parasite Leishmania. Science 226: 977–979.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • A. Kharazmi
    • 1
  • A. L. Sørensen
    • 1
  • H. Nielsen
    • 1
  1. 1.State Serum Institute Department of Clinical MicrobiologyCopenhagenDenmark

Personalised recommendations