A study of the GABAergic mechanisms of the neuropsychotropic action of neuroglutam

作者：Tyurenkov I N; Bagmetova V V^*; Robertus A I; Vasil'eva E V; Kovalev G I

来源：Neurochemical Journal, 2015, 9(2): 116-126.

DOI：10.1134/S1819712415010134

• neuroglutam
• derivatives of glutamic acid
• antidepressants
• anxiolytics
• neuroprotectors
• GABA
• GABA receptors
• radioligand binding in vitro and ex vivo

To study the mechanisms of the action of neuroglutam (beta-phenylglutamic acid hydrochloride, RGPU-135), which is a drug with antidepressant and anxiolytic activities, we examined the influence of the antagonist of GABA(A) receptors bicuculline (1 mg/kg) and the antagonist of GABA(B) receptors phaclofen (2 mg/kg) on the type and strength of the effects of neuroglutam (26 mg/kg) in behavioral tests. Anxiolytic effects were examined in the open-field test and dark-light box; antidepressant effects were examined in the tail-suspension test. During combined treatment with neuroglutam and bicuculline, anxiolytic and antidepressant effects of neuroglutam did not occur, i.e., development of these effects requires activation of GABA(A) receptors. Phaclofen counteracted the antidepressant effect of neuroglutam, which, to a certain degree is related to activation of GABA(B) receptors. Neuroglutam (26-650 mg/kg) suppressed seizures that were induced by the blockers of GABA(A) receptors picrotoxin (5 mg/kg) and pentylenetetrazol (90 mg/kg), which reflects its capacity to influence this channel. Analysis of the neuroglutam influence (10-10-10-4 M) on the rat brain GABA(A) and GABA(B) receptors by the method of radioligand binding in vitro using tritiated [G(3)-H]SR95531 (for GABA(A)) and [G(3)-H](-)Baclofen (for GABA(B) receptors) did not reveal direct interaction of neuroglutam with these receptors. Subchronic systemic administration of neuroglutam (26 mg/kg, daily for 5 days) to rats induced an increase in the density of GABA(A) receptors in the prefrontal cortex, which points to its capacity to modulate the expression of GABA(A) receptors. These data suggest that one of the aspects of the neuropsychotropic effects of neuroglutam is interaction with the GABAergic neurotransmitter system.

• 出版日期2015-4