Antimalarial properties of imipramine and amitriptyline
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Abstract:
Dietary riboflavin deficiency is known to diminish malarial parasitemia. In this study, we determined whether imipramine and amitriptyline, drugs which inhibit riboflavin metabolism, have antimalarial efficacy. In addition, we evaluated whether these drugs, like other antimalarial agents, increase the hemolytic response to ferriprotoporphyrin IX (FP). The growth of Plasmodium falciparum (FCR3) in the absence and presence of these drugs (10 to 75 microM) was measured by determining (3H)hypoxanthine uptake by intra-erythrocytic parasites for 48 h in RPMI 1640 medium. The uptake of (3H)hypoxanthine was significantly reduced in a dose-dependent manner by both imipramine and amitriptyline. The IC50 values of imipramine and amitriptyline at 48 h were 56 and 45 microM, respectively. Both drugs enhanced hemolysis induced by FP (10 or 20 microM). No hemolysis by these drugs was detected in the absence of FP. It is concluded that the tricyclic antidepressants, imipramine and amitriptyline, possess substantial antimalarial properties.
Insights
Tricyclic antidepressants imipramine and amitriptyline show antimalarial efficacy by inhibiting Plasmodium falciparum growth. These drugs also enhance the hemolytic response to ferriprotoporphyrin IX, indicating potential antimalarial properties.
Area of Science:
- Pharmacology
- Infectious Diseases
- Biochemistry
Background:
- Dietary riboflavin deficiency is linked to reduced malaria parasite levels.
- Imipramine and amitriptyline are known to inhibit riboflavin metabolism.
- Investigating novel antimalarial agents is crucial for combating drug resistance.
Purpose of the Study:
- To determine the antimalarial efficacy of imipramine and amitriptyline.
- To evaluate the effect of these drugs on the hemolytic response to ferriprotoporphyrin IX (FP).
- To explore the potential of tricyclic antidepressants as antimalarial treatments.
Main Methods:
- Plasmodium falciparum (FCR3) growth was assessed by measuring (3H)hypoxanthine uptake in the presence of varying drug concentrations (10-75 microM).
- The hemolytic response to ferriprotoporphyrin IX (FP) was measured with and without imipramine and amitriptyline.
- Drug efficacy was quantified using IC50 values.
Main Results:
- Both imipramine and amitriptyline significantly inhibited Plasmodium falciparum growth in a dose-dependent manner.
- The IC50 values for imipramine and amitriptyline were 56 microM and 45 microM, respectively.
- The drugs enhanced FP-induced hemolysis, with no hemolysis observed in the absence of FP.
Conclusions:
- Imipramine and amitriptyline exhibit significant antimalarial properties.
- These tricyclic antidepressants demonstrate potential as novel therapeutic agents against malaria.
- The drugs' ability to enhance ferriprotoporphyrin IX-induced hemolysis warrants further investigation.