Antimalarial properties of imipramine and amitriptyline

Conference · Fri Feb 28 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5383604

Dutta, P; Siegel, L; Pinto, J; Meshnick, S

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-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANTIDEPRESSANTS
AROMATICS
AZAARENES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CENTRAL NERVOUS SYSTEM AGENTS
DISEASES
DRUGS
ERYTHROCYTES
HEMOLYSIS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
HYPOXANTHINE
IMIPRAMINE
INFECTIOUS DISEASES
INHIBITION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LYSIS
MALARIA
MATERIALS
METABOLISM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASITIC DISEASES
PATHOLOGICAL CHANGES
PSYCHOTROPIC DRUGS
PURINES
RIBOFLAVIN
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VITAMIN B GROUP
VITAMINS