Antimalarial effect of agmatine on Plasmodium berghei K173 strain

Acta Pharmacol Sin. 2003 Sep;24(9):918-22.

Abstract

Aim: To study the antimalarial effect of agmatine (Agm) on chloroquine-susceptible Plasmodium berghei K173 strain (S strain) and the P berghei K173 resistant strain (R strain).

Methods: The antimalarial effects of Agm on P berghei K173 S strain and R strain were evaluated by Peters 4-d suppression test in mice.

Results: Agm (12.5-200 mg/kg, ig, daily) decreased the parasitemia for both P berghei K173 S strain (IC(50)=139 mg/kg) and R strain (IC(50)=126 mg/kg) in mice. Subcutaneous injection (sc) of Agm (5-40 mg/kg, tid) showed relatively stronger antimalarial effect than intragastric gavage (IC(50)=30 mg/kg ) in P berghei K173 S strain. Spermidine antagonized the antimalarial effect of Agm for P berghei K173 S strain and R strain. Agm did not reverse the chloroquine resistance of P berghei K173 S strain. dl-alpha-Difluoromethylornithine (DFMO, sc) decreased the parasitemia of P Berghei K173 S strain and this effect was antagonized by spermidine.

Conclusion: Agm has an antimalarial effect and the mechanism is related to its inhibition of polyamine synthesis.

MeSH terms

  • Agmatine / pharmacology*
  • Agmatine / therapeutic use
  • Animals
  • Antimalarials / pharmacology*
  • Antimalarials / therapeutic use
  • Chloroquine / pharmacology
  • Disease Models, Animal
  • Drug Resistance
  • Eflornithine / pharmacology
  • Female
  • Malaria / drug therapy*
  • Male
  • Mice
  • Ornithine Decarboxylase Inhibitors
  • Parasitemia / drug therapy
  • Parasitic Sensitivity Tests
  • Plasmodium berghei / drug effects*

Substances

  • Antimalarials
  • Ornithine Decarboxylase Inhibitors
  • Agmatine
  • Chloroquine
  • Eflornithine