(R)-Primaquine
(R)-Primaquine ((−)-Primaquine) is the R-configured enantiomer of Primaquine (HY-12651A). (R)-Primaquine is an antimalarial agent. The Vmax and Km values of (R)-Primaquine metabolism by recombinant human CYP2D6 are 0.42 μmol/min/mg and 21.6 μM, respectively. (R)-Primaquine can be used in malaria-related research.
For research use only. We do not sell to patients.
- CAS No.: 57152-56-4
- Formula: C15H21N3O
- Molecular Weight:259.35
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
(R)-Primaquine (20 μM; 120 min) is metabolized by recombinant human CYP2D6 with a Vmax of 0.42 μmol/min/mg and Km of 21.6 μM, preferentially forming 4-OH-PQ (22% of total conversion), higher levels of 3-OH-PQ, and specific dihydroxylated metabolites, while being depleted at a slower rate (30% depletion of 20 μM in 120 min) than (+)-(S)-primaquine[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
(R)-Primaquine (10-160 mg/kg; p.o.; daily administration; for 3 consecutive days) exhibits causal prophylactic activity against liver-stage Plasmodium berghei infection induced by sporozoites in ICR mice, with an ED80 of 63.7 mg/kg/day, and achieves 100% protection at 80 mg/kg/day.[3]
(R)-Primaquine (2-10 mg/kg; p.o.; daily administration; for 21 consecutive days) shows no efficacy against Pneumocystis carinii infection in immunosuppressed BALB/c mice when administered at the highest dose of 10 mg/kg/day for 21 days[3].
(R)-Primaquine (6.25-12.5 mg/kg; intraperitoneal injection; twice daily for 7 consecutive days) causes only mild hemolysis in G6PD-deficient human erythrocytes transplanted into NOD-SCID mice. At doses up to 12.5 mg/kg/day administered for 7 days, its hemolytic activity is significantly lower than that of (S)-primaquine[3].
(R)-Primaquine (4.86 mg/kg; p.o.; once daily; for 3 consecutive days) is well tolerated in female Beagle dogs after administration at a dose of 4.86 mg/kg/day for 3 days, with no significant systemic toxicity, methemoglobinemia, or organ damage observed[3].
(R)-Primaquine (1.3-4.5 mg/kg/day; oral administration; once daily; for 7 consecutive days) induces dose-dependent increases in methemoglobin, reticulocytes, and alanine transaminase (ALT) in healthy G6PD-normal rhesus monkeys, and no severe reversible hepatotoxicity is observed at doses up to 4.5 mg/kg/day[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Swiss Webster (male, 18 to 20 g, intraperitoneally inoculated with Plasmodium berghei NK-65 strain parasitized red blood cells)[3]
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Dosage:11.1 mg/kg/day; 33.3 mg/kg/day; 100 mg/kg/day
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Administration:p.o.; daily; 3 days (days 0 to 2)
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Result:At 100 mg/kg/day, achieved 100% parasitemia suppression and cured 2/5 mice by day 28.
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Animal Model:ICR (female, inoculated with Plasmodium berghei ANKA strain sporozoites isolated from Anopheles dirus mosquitoes)[3]
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Dosage:10 mg/kg/day; 80 mg/kg/day; 160 mg/kg/day
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Administration:p.o.; daily; 3 days (days -1 to 1)
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Result:Resulted in 0% of mice surviving to day 31 at 10 mg/kg/day.
Resulted in 100% of mice surviving to day 31 at 80 mg/kg/day.
Resulted in 80% of mice surviving to day 31 (1/5 mice died due to toxicity) at 160 mg/kg/day.
Had an ED80 (80% effective dose) of 63.7 mg/kg/day for 3 days.
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Animal Model:BALB/c (female, 6 to 8 weeks old, immunosuppressed with dexamethasone, transtracheally inoculated with Pneumocystis carinii organisms)[3]
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Dosage:2 mg/kg/day; 5 mg/kg/day; 10 mg/kg/day
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Administration:p.o.; daily; 21 days via drinking water
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Result:Resulted in 0/10 mice cured of P. carinii infection at all tested doses.
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Animal Model:NOD.CB17-Prkdcscid/J (NOD-SCID) (female, 8 to 9 weeks old, intraperitoneally transfused with African variant G6PD-deficient human red blood cells)[3]
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Dosage:6.25 mg/kg/day; 12.5 mg/kg/day
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Administration:i.p.; twice daily; 7 days
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Result:Produced substantially less erythrocyte loss than (S)-Primaquine; no significant loss at 6.25 mg/kg/day versus PBS.
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Animal Model:Beagle (female)[3]
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Dosage:4.86 mg/kg/day
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Administration:p.o.; daily; 3 days
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Result:All animals survived; body-weight loss was approximately 3-8%, with clinical chemistry and hematology remaining near baseline.
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Animal Model:Macaca mulatta (Indian-origin, male, non-malaria-naive, median age 10.8 years, median weight 9.3 kg, G6PD-normal)[4]
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Dosage:1.3 mg/kg/day; 3.0 mg/kg/day; 4.5 mg/kg/day
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Administration:p.o.; daily; 7 days
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Result:Generally tolerated at 1.3 and 3.0 mg/kg/day; caused severe reversible hepatotoxicity in 2/3 animals at 4.5 mg/kg/day.
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Animal Model:Macaca mulatta (Indian-origin, malaria-naive, median age 4 years, median weight 5.4 kg, G6PD-normal)[4]
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Dosage:1.3 mg/kg/day (in combination with 10 mg/kg/day Chloroquine (HY-17589A) base); 0.6 mg/kg/day (in combination with 10 mg/kg/day chloroquine base)
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Administration:p.o.; daily; 7 days
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Result:Produced lower mean methemoglobin increases than (S)-Primaquine at 1.3 and 3.0 mg/kg/day.
Chemical Information
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CAS No. 57152-56-4
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Molecular Weight 259.35
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Formula C15H21N3O
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SMILES
COC(C=C1N[C@@H](CCCN)C)=CC2=C1N=CC=C2
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Synonyms
(-)-Primaquine
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Fasinu PS, et al. Enantioselective metabolism of primaquine by human CYP2D6. Malaria journal. 2014 Dec 17;13:507. [Content Brief]
[2]. Chairat K, et al. Enantiospecific pharmacokinetics and drug-drug interactions of primaquine and blood-stage antimalarial drugs. The Journal of antimicrobial chemotherapy. 2018 Nov 01;73(11):3102-3113. [Content Brief]
[3]. Nanayakkara NP, et al. Scalable preparation and differential pharmacologic and toxicologic profiles of primaquine enantiomers. Antimicrobial agents and chemotherapy. 2014 Aug;58(8):4737-44. [Content Brief]
[4]. Saunders D, et al. Pharmacokinetics and pharmacodynamics of (+)-primaquine and (-)-primaquine enantiomers in rhesus macaques (Macaca mulatta). Antimicrobial agents and chemotherapy. 2014 Dec;58(12):7283-91. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)