Evaluation of antidepressant-like and anxiolytic-like activity of purinedione-derivatives with affinity for adenosine A2Areceptors in mice.
BACKGROUND
It has recently been suggested that the adenosine A2Areceptor plays a role in several animal models of depression. Additionally, A2Aantagonists have reversed behavioral deficits and exhibited a profile similar to classical antidepressants.


METHODS
In the present study, imidazo- and pyrimido[2,1-f]purinedione derivatives (KD 66, KD 167, KD 206) with affinity to A2Areceptors but poor A1affinity were evaluated for their antidepressant- and anxiolytic-like activity. The activity of these derivatives was tested using a tail suspension and forced swim test, two widely-used behavioral paradigms for the evaluation of antidepressant-like activity. In turn, the anxiolytic activity was evaluated using the four-plate test.


RESULTS
The results showed the antidepressant-like activity of pyrimido- and imidazopurinedione derivatives (i.e. KD 66, KD 167 and KD 206) in acute and chronic behavioral tests in mice. KD 66 revealed an anxiolytic-like effect, while KD 167 increased anxiety behaviors. KD 206 had no effect on anxiety. Furthermore, none of the tested compounds increased locomotor activity.


CONCLUSIONS
Available data support the proposition that the examined compounds with adenosine A2Areceptor affinity may be an interesting target for the development of antidepressant and/or anxiolytic agents.
Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland. Electronic address: anna.dziubina@uj.edu.pl.
Anna
A
Dziubina
Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
Karina
K
Szmyd
Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
Małgorzata
M
Zygmunt
Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
Jacek
J
Sapa
Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
Magdalena
M
Dudek
Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
Barbara
B
Filipek
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Anna
A
Drabczyńska
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Michał
M
Załuski
Department of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland.
Karolina
K
Pytka
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Katarzyna
K
Kieć-Kononowicz
D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D003863:Depression / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007103:Immobilization / Q000379:methods / Q000523:psychology; D008297:Male; D051379:Mice; D058905:Purinergic Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D058905:Purinergic Agents
Adenosine A(2A) receptor; Antidepressant activity; Imidazo[2,1-f]purinediones; Pyrimido[2,1-f]purinediones