Effects of acute administration of mazindol on brain energy metabolism in adult mice.

Abstract

OBJECTIVES:

Mazindol is a sympathomimetic amine, widely used as an anorectic agent in the treatment of obesity. This drug causes psychostimulant effects because of its pharmacological profile similar to amphetamine, acting like a monoamine reuptake inhibitor. However, the mechanisms underlying the action of mazindol are still not clearly understood.

METHODS:

Swiss mice received a single acute administration of mazindol (0.25, 1.25 and 2.5 mg/kg, ip) or saline. After 2 h, the animals were killed by decapitation; the brain was removed and used for the evaluation of activities of mitochondrial respiratory chain complexes, Krebs cycle enzymes and creatine kinase.

RESULTS:

Acute administration of mazindol decreased complex I activity only in the hippocampus. Complex IV activity was increased in the cerebellum (2.5 mg/kg) and cerebral cortex (0.25 mg/kg). Citrate synthase activity was increased in the cerebellum (1.25 mg/kg) and cerebral cortex (1.25 mg/kg), and creatine kinase activity was increased in the cerebellum (1.25 mg/kg).

CONCLUSION:

We suggest that the inhibition of complex I in the hippocampus only and activation of complex IV, citrate synthase and creatine kinase occurs because of a stimulus effect of mazindol in the central nervous system, which causes a direct impairment on energy metabolism.

• Authors: Cinara Ludvig Gonçalves, Giselli Scaini, Gislaine Tezza Rezin, Isabela Casagrande Jeremias, Gisele Daiane Bez, Juliana Felipe Daufenbach, Lara Mezari Gomes, Gabriela Kozuchovski Ferreira, Alexandra Ioppi Zugno, Emilio Luiz Streck
• Journal: Acta neuropsychiatrica (Acta Neuropsychiatr) Vol. 26 Issue 3 Pg. 146-54 (Jun 2014) ISSN: 1601-5215 [Electronic] England
• PMID: 25142190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Central Nervous System Stimulants
• Mazindol

Topics

• Animals
• Brain (drug effects, metabolism)
• Central Nervous System Stimulants (administration & dosage, pharmacology, therapeutic use)
• Energy Metabolism (drug effects)
• Male
• Mazindol (administration & dosage, pharmacology, therapeutic use)
• Mice
• Obesity (drug therapy, metabolism)