Antimalarial properties of imipramine and amitriptyline
This laboratory has previously demonstrated that imipramine (IM) and amitriptyline (AM), inhibit the conversion of riboflavin to its coenzymic derivatives. Several other laboratories have shown that dietary riboflavin deficiency is protective against malarial infection. In the present investigation, the authors determined whether IM and AM exert antimalarial effects similar to that of riboflavin deficiency, as they have hypothesized. In addition, they evaluated whether these drugs, like other antimalarial agents, increase the hemolytic response to ferriprotoporphyrin IX (FP). The growth of P. falciparum (FCR3) in the absence or presence of these drugs (80 ..mu..M) was measured by incubating parasitized erythrocytes for 48 h in RPMI 1640 medium. Parasitemia was determined by counting erythrocyte smears and monitoring (/sup 3/H)hypoxanthine uptake. With no drug, parasitemia was 20.3 +/- 5.3%, whereas in the presence of IM and AM, parasitemia was reduced to 7.3 +/- 0.8% and 13.6 +/- 2.8%, respectively. The uptake of (/sup 3/H)hypoxanthine was reduced to 47 +/- 3.6% and 54 +/- 2.9% of control by IM and AM, respectively. Assays of hemolysis were conducted by incubating 0.5% RBC suspension in NaCl-Tris buffer for 3 h at 37/sup 0/C with variable concentrations of drugs and/or FP (1-7 ..mu..M). Both drugs at 10 to 100 ..mu..M significantly enhanced hemolysis induced by FP. No hemolysis by these drugs was detected in the absence of FP. It is concluded that the tricyclic antidepressants, IM and AM, possess substantial antimalarial properties, thereby supporting the hypothesis that drugs which interfere with riboflavin metabolism should also provide protection against malaria.
- Research Organization:
- Cornell Univ. Medical College, New York, NY
- OSTI ID:
- 5383604
- Report Number(s):
- CONF-8604222-; TRN: 86-026707
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTIDEPRESSANTS
BIOLOGICAL EFFECTS
ERYTHROCYTES
HEMOLYSIS
IMIPRAMINE
RIBOFLAVIN
METABOLISM
HYPOXANTHINE
INHIBITION
MALARIA
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
AROMATICS
AZAARENES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CENTRAL NERVOUS SYSTEM AGENTS
DISEASES
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INFECTIOUS DISEASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LYSIS
MATERIALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASITIC DISEASES
PATHOLOGICAL CHANGES
PSYCHOTROPIC DRUGS
PURINES
VITAMIN B GROUP
VITAMINS
550901* - Pathology- Tracer Techniques