Karolina Bogatko1, Ewa Poleszak1, Aleksandra Szopa1, Elżbieta Wyska2, Piotr Wlaź3, Katarzyna Świąder1, Aleksandra Wlaź4, Urszula Doboszewska3, Karol Rojek1, Anna Serefko1. 1. Department of Applied Pharmacy, Medical University of Lublin, Lublin, Poland. 2. Department of Pharmacokinetics and Physical Pharmacy, Collegium Medicum, Jagiellonian University, Kraków, Poland. 3. Department of Animal Physiology, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Lublin, Poland. 4. Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
Abstract
OBJECTIVE: The main goal of our study was to investigate whether a selective antagonism of the adenosine A1 or A2A receptors is able to enhance the antidepressant activity of commonly prescribed drugs. MATERIALS AND METHODS: All experiments were carried out on male Albino Swiss mice. The forced swim test and the tail suspension test were used to evaluate the antidepressant-like potential. Drug concentrations in animals' serum and brains were measured by high-performance liquid chromatography. KEY FINDINGS: The antidepressant potential of moclobemide (1.5 mg/kg), venlafaxine (1 mg/kg) and bupropion (10 mg/kg) was enhanced by a co-administration with 3,7-dimethyl-1-propargylxanthine (DMPX; an antagonist of adenosine A2A receptors; 3 mg/kg) or 8-cyclopentyl-1,3-dipropylxanthine (an antagonist of adenosine A1 receptors; 1 mg/kg). However, significant interactions between the tested substances were detected only in the experiments with DMPX. The nature of the observed interplays is rather pharmacodynamic than pharmacokinetic, because neither serum nor brain concentrations of the used drugs were significantly increased. CONCLUSIONS: Blockage of the adenosine receptors (particularly the A2A subtypes) could be considered in future as a novel, promising part of the combined antidepressant therapy. However, further studies on this subject are needed.
OBJECTIVE: The main goal of our study was to investigate whether a selective antagonism of the adenosine A1 or A2A receptors is able to enhance the antidepressant activity of commonly prescribed drugs. MATERIALS AND METHODS: All experiments were carried out on male Albino Swiss mice. The forced swim test and the tail suspension test were used to evaluate the antidepressant-like potential. Drug concentrations in animals' serum and brains were measured by high-performance liquid chromatography. KEY FINDINGS: The antidepressant potential of moclobemide (1.5 mg/kg), venlafaxine (1 mg/kg) and bupropion (10 mg/kg) was enhanced by a co-administration with 3,7-dimethyl-1-propargylxanthine (DMPX; an antagonist of adenosine A2A receptors; 3 mg/kg) or 8-cyclopentyl-1,3-dipropylxanthine (an antagonist of adenosine A1 receptors; 1 mg/kg). However, significant interactions between the tested substances were detected only in the experiments with DMPX. The nature of the observed interplays is rather pharmacodynamic than pharmacokinetic, because neither serum nor brain concentrations of the used drugs were significantly increased. CONCLUSIONS: Blockage of the adenosine receptors (particularly the A2A subtypes) could be considered in future as a novel, promising part of the combined antidepressant therapy. However, further studies on this subject are needed.
Authors: Renata L de Oliveira; Guilherme T Voss; Jaini J Paltian; Mikaela P Pinz; Marina Laura C P Torres; Michele P Moreira; Marina C Dilelio; Claudio C Silveira; Ethel A Wilhelm; Cristiane Luchese Journal: Metab Brain Dis Date: 2019-06-08 Impact factor: 3.584