Phenibut, Semax and GIZh-290 Modulate Cortical mGluII Receptors in an Attention Deficit Model in Mice

In our previous experiments, it was found that the nootropic drugs piracetam (200 mg/kg/day, intraperitoneally), pantogam (100), pantogam active (200), phenibut (70), semax (0.6), as well as a new derivative of racetam GIZh-290 (3) and the comparison drug atomoxetine (3.0) as a result of subchronic administration, attention stability to new objects is restored in the “closed enriched cross maze” test, showing selectivity of the effect in relation to a subpopulation of CD-1 mice with an initially low attention index (ED-Low). In this study, the effect of nootropics on metabotropic glutamate receptors (mGluRII) in the prefrontal cortex of these mice was studied using the receptor binding of a specific radioligand [G-³H]LY354740. It was found that the density (B_max) of mGluII receptors in the brains of subpopulation with the ED-Low phenotype was 11–25% lower than in subpopulation with the ED-High phenotype. None of the drugs had an effect on these receptors in the subpopulation with the ED-High phenotype, whereas phenibut, semax and GIZh-290 showed efficacy with respect to the ED-Low phenotype, increasing B_max values by 60, 19 and 22%, respectively. Thus, it was shown for the first time that mGluRII are involved in the pathogenesis of attention impairment, and the ability of phenibut, semax and GIZh-290 (2,6-dimethylanilide (2-oxo-4-phenylpyrrolidine-1-yl) acetate to selectively normalize the reduced density of these receptors indicates the prospects of their use in as a drugs for the treatment of attention deficit disorder.