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Pathway Description
Primaquine Action Pathway
Plasmodium falciparum
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-02-09
Last Updated: 2023-10-25
Primaquine is an minoquinoline antimalarial is a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. It is the essential co-drug with chloroquine in treating all cases of malaria.
In the blood, malaria parasites break down a part of the red blood cells known as haemoglobin. When this happens haemoglobin is divided into two parts; haem and globin. Haem is toxic to the malaria parasite. To prevent it from being damaged, the malaria parasite produces an chemical which converts the toxic haem into a non-toxic product. Primaquine acts by interfering with a part of the parasite (mitochondria) that is responsible for supplying it with energy. Without energy the parasite dies. Primaquine's mechanism of action is not well understood. It may be acting by generating reactive oxygen species or by interfering with the electron transport in the parasite. Also, although its mechanism of action is unclear, primaquine may bind to and alter the properties of protozoal DNA.
References
Primaquine Pathway References
Mihaly GW, Ward SA, Edwards G, Nicholl DD, Orme ML, Breckenridge AM: Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size. Br J Clin Pharmacol. 1985 Jun;19(6):745-50. doi: 10.1111/j.1365-2125.1985.tb02709.x.
Pubmed: 4027117
ALVING AS, ARNOLD J, HOCKWALD RS, CLAYMAN CB, DERN RJ, BEUTLER E, FLANAGAN CL: Potentiation of the curative action of primaquine in vivax malaria by quinine and chloroquine. J Lab Clin Med. 1955 Aug;46(2):301-6.
Pubmed: 13242948
Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ: Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg. 2006 Sep;75(3):402-15.
Pubmed: 16968913
Cohen RJ, Sachs JR, Wicker DJ, Conrad ME: Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam. N Engl J Med. 1968 Nov 21;279(21):1127-31. doi: 10.1056/NEJM196811212792102.
Pubmed: 5686480
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Pubmed: 11181487
Bapiro TE, Andersson TB, Otter C, Hasler JA, Masimirembwa CM: Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells. Eur J Clin Pharmacol. 2002 Nov;58(8):537-42. doi: 10.1007/s00228-002-0512-z. Epub 2002 Oct 2.
Pubmed: 12451431
Dorn A, Vippagunta SR, Matile H, Jaquet C, Vennerstrom JL, Ridley RG: An assessment of drug-haematin binding as a mechanism for inhibition of haematin polymerisation by quinoline antimalarials. Biochem Pharmacol. 1998 Mar 15;55(6):727-36. doi: 10.1016/s0006-2952(97)00510-8.
Pubmed: 9586944
Fitch CD: Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004 Mar 5;74(16):1957-72. doi: 10.1016/j.lfs.2003.10.003.
Pubmed: 14967191
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Pubmed: 29126136
Michelson AM, Orkin SH: The 3' untranslated regions of the duplicated human alpha-globin genes are unexpectedly divergent. Cell. 1980 Nov;22(2 Pt 2):371-7. doi: 10.1016/0092-8674(80)90347-5.
Pubmed: 7448866
Wilson JT, Wilson LB, Reddy VB, Cavallesco C, Ghosh PK, deRiel JK, Forget BG, Weissman SM: Nucleotide sequence of the coding portion of human alpha globin messenger RNA. J Biol Chem. 1980 Apr 10;255(7):2807-15.
Pubmed: 6244294
Liebhaber SA, Goossens MJ, Kan YW: Cloning and complete nucleotide sequence of human 5'-alpha-globin gene. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7054-8. doi: 10.1073/pnas.77.12.7054.
Pubmed: 6452630
Marotta CA, Forget BG, Cohen-Solal M, Weissman SM: Nucleotide sequence analysis of coding and noncoding regions of human beta-globin mRNA. Prog Nucleic Acid Res Mol Biol. 1976;19:165-75.
Pubmed: 1019344
Lawn RM, Efstratiadis A, O'Connell C, Maniatis T: The nucleotide sequence of the human beta-globin gene. Cell. 1980 Oct;21(3):647-51. doi: 10.1016/0092-8674(80)90428-6.
Pubmed: 6254664
Wood ET, Stover DA, Slatkin M, Nachman MW, Hammer MF: The beta -globin recombinational hotspot reduces the effects of strong selection around HbC, a recently arisen mutation providing resistance to malaria. Am J Hum Genet. 2005 Oct;77(4):637-42. doi: 10.1086/491748. Epub 2005 Aug 29.
Pubmed: 16175509
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