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1

Ifenprodil and NMDA ligands

100%
Wosko S., Szopa A., Serefko A., Poleszak E.
Acta Neurobiologiae Experimentalis
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2013
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tom 73
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nr 1
Depression is one of the most common affective disorders. According to the World Health Organization (WHO), it is currently the fourth major global health problem (Kessler et al. 2003). The growing number of people suffering from depression has motivated the scientists to search for new antidepressant drugs. Since numerous studies revealed that NMDA receptor may be involved in the mechanism of action of the antidepressant agents, modulation of the NMDA receptor function by different ligands has been taken into consideration. There are some promising results demonstrating the antidepressant activity of the antagonists binding to the polyamine site of the NMDA receptor complex. Ifenprodil belongs to a family of the selective, atypical non-competitive antagonists of the NMDA receptors. It acts via inhibition of the polyamine binding site of the NR2B subunit (Williams 1993). An antidepressantlike effect of ifenprodil was observed in several behavioral studies, for example in the forced swimming test (Carter et al. 1990, Williams 1993, Layer et al. 1995, Scolnik 1999, Paoletti and Neyton 2007). It was shown that its antidepressant-like activity is increased by other antidepressant drugs (imipramine and fluoxetine). The aim of our work was to evaluate the antidepressant activity of the joint administration of ifenprodil and NMDA ligands in the mouse forced swimming test (FST). The experiments were carried out on male Albino Swiss mice. In order to avoid the risk of obtaining the false positive/negative effects in the FST test caused by a possible influence of the tested substances on the locomotor activity, the spontaneous locomotor activity was measured. The obtained results demonstrated that ifenprodil at the dose of 10 mg/ kg enhances the antidepressant-like effect of the following NMDA receptor ligands: a competitive NMDA receptor antagonist – CGP 37849 (0.312 mg/kg), an antagonist at glycine site – L-701,324 (1 mg/kg) and a non-competitive antagonist at phencyclidyne – MK801 (0.05 mg/kg). However, it did not potentiate the antidepressant activity of the inorganic modulators of the NMDA receptor complex, such as Zn2+ (2.5 mg/kg) and Mg2+ (10 mg/kg). Treatment with the tested agents did not influence the locomotor activity. In conclusion, our findings indicated that antidepressant-like activity of ifenprodil is connected with serotoninergic and glutamatergic system.
2

The effect of caffeine on the activity of NMDA receptor ligands in the forced swim test in mice

100%
Poleszak E., Szopa A., Serefko A., Wosko S.
Acta Neurobiologiae Experimentalis
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2014
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tom 74
|
nr 3
Depression is one of the most frequent chronic and life-debilitating health problems in the world. Though its epidemiology, risk factors and development have been continuously studied for decades, the optimal treatment of the depressed patients still remains an important clinical dilemma. The conventional antidepressant therapy is not sufficient due to the common ineffectiveness and adverse reactions. The search for better alternatives seems to be crucial. Recently, much consideration has been given to both totally novel chemical compounds as well as to the unique combinations of the well-known drugs. The use of the NMDA receptor ligands, particularly in co-administration with other agents exerting the antidepressant activity, emerged amongst the new ideas. The main objective of our study was to evaluate the influence of caffeine on the antidepressant-like activity of various NMDA receptor modulators. The antidepressant-like effect was assessed by the forced swim test in mice. The obtained results demonstrated the significant interaction between caffeine (5 mg/kg) and the following NMDA receptor ligands: CGP 37849 (0.312 mg/kg), L-701,324 (1 mg/kg) and D-cycloserine (2.5 mg/ kg). Interaction between caffeine and the inorganic modulators, i.e. Zn2+ (2.5 mg/kg) and Mg2+ (10 mg/kg), was not considered as significant. The antidepressant-like potential of the NMDA receptor ligands (except for Zn2+ and Mg2+) given concomitantly with caffeine was reinforced. The possible mechanism of the observed interaction may involve the influence of caffeine on the glutamatergic system.
3

The influence of DMPX on the activity of common antidepressants

76%
Poleszak E., Serefko A., Szopa A., Wosko S., Bogutko K., Swiader K., Wlaz P.
Acta Neurobiologiae Experimentalis
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2015
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tom 75
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nr Supl.
BACKGROUND AND AIMS: Though depression is known as one of the most frequent chronic health problems in the world, the optimal treatment of the depressed patients remains an important challenge. Due to serious adverse reactions and common ineffectiveness, the conventional antidepressant therapy is usually not sufficient. The identification of the best treatment strategies and development of new, safer, and more effective ones are crucial. Literature data confirm participation of adenosine neurotransmission in the development of depression. Adenosine, which is responsible for the suppressed release of serotonin, noradrenalin, and dopamine, contributes to a decrease of neuronal excitability. The main objective of our study was to investigate an antidepressant activity of a joint administration of adenosine A2A receptor antagonist DMPX (3,7-dimethyl-1-propargylxanthine) and the common antidepressant drugs: imipramine, reboxetine, escitalopram, tianeptine, venlafaxine, moclobemide, and agomelatine. METHODS: The experiments were carried out on male Albino Swiss mice. The antidepressant-like effect was assessed by the forced swim test. In order to avoid the risk of obtaining the false positive/negative effects, the spontaneous locomotor activity was measured as well. RESULTS: The obtained results demonstrated that DMPX at the dose of 3 mg/kg significantly enhanced the antidepressant-like effect of imipramine (15 mg/kg), reboxetine (2.5 mg/kg), escitalpram (2 mg/kg), tianeptine (15 mg/kg), venlafaxine (1 mg/kg), moclobemide (1.5 mg/kg), and agomelatine (20 mg/kg). None of the used combinations changed the overall spontaneous locomotor activity of the animals. CONCLUSION: Forced swim test outcomes indicated a synergistic action of adenosine A2A receptor antagonist in combination with the tested antidepressants.
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