Behavioral and neurochemical effects of the new racetam derivative GIZh-290 were studied in a mouse attention deficit model (the ED-Low animals subpopulation selected during preliminary behavioral typing in the “closed enriched cross maze” test). Subchronic administration of GIZh-290 (1 mg/kg, 3 mg/kg and 5 mg/kg, intraperitoneally, for 6 days), increased the initially low level of attention in ED-Low animals; the highest selectivity was observed at a dose of 3 mg/kg. Radioligand analysis showed that at this dose, the drug changed density (Bmax) of D2 and GABAB receptors as markers in the pre-frontal cortex of the ED-Low subpopulation to Bmax values observed in the ED-High subpopulation. In the prefrontal cortex of the ED-Low rodents treated with GIZh-290 in dose of 3 mg/kg, there was a normalization of tissue concentrations of both dopamine itself (DA) and its intra- and extracellular metabolites (DOPA/DA and HVA/DA). The obtained results indicate the effectiveness of the studied drug for pharmacotherapy of attention deficit in experimental modeling and impact on potential molecular targets identified in the study.
Kovalev G.I., Sukhorukova N.A., Vasileva E.V., Kondrakhin E.A., Salimov R.M., Narkevich V.B., Kudrin V.S. (2022) Behavioral and neuroreceptor effects of the racetam derivative GIZh-290 in mouse experimental attention deficit model. Biomeditsinskaya Khimiya, 68(5), 367-374.
Kovalev G.I. et al. Behavioral and neuroreceptor effects of the racetam derivative GIZh-290 in mouse experimental attention deficit model // Biomeditsinskaya Khimiya. - 2022. - V. 68. -N 5. - P. 367-374.
Kovalev G.I. et al., "Behavioral and neuroreceptor effects of the racetam derivative GIZh-290 in mouse experimental attention deficit model." Biomeditsinskaya Khimiya 68.5 (2022): 367-374.
Kovalev, G. I., Sukhorukova, N. A., Vasileva, E. V., Kondrakhin, E. A., Salimov, R. M., Narkevich, V. B., Kudrin, V. S. (2022). Behavioral and neuroreceptor effects of the racetam derivative GIZh-290 in mouse experimental attention deficit model. Biomeditsinskaya Khimiya, 68(5), 367-374.
References
Faraone S.V., Banaschewski T., Coghill D., Zheng Y., Biederman J., Bellgrove M.A., Newcorn J.H., Gignac M., Al Saud N.M., Manor I., Rohde L.A., Yang L., Cortese S., Almagor D., Stein M.A., Albatti T.H., Aljoudi H.F., Alqahtani M.M.J., Asherson P., Atwoli L., Bölte S., Buitelaar J.K., Crunelle C.L., Daley D., Dalsgaard S., Döpfner M., Espinet S., Fitzgerald M., Franke B., Gerlach M., Haavik J., Hartman C.A., Hartung C.M., Hinshaw S.P., Hoekstra P.J., Hollis C., Kollins S.H., Kooij J.J.S., Kuntsi J., Larsson H., Li T., Liu J., Merzon E., Mattingly G., Mattos P., McCarthy S., Mikami A.Y., Molina B.S.G., Nigg J.T., Purper-Ouakil D., Omigbodun O.O., Polanczyk G.V., Pollak Y., Poulton A.S., Rajkumar R.P., Reding A., Reif A., Rubia K., Rucklidge J., Romanos M., Ramos-Quiroga J.A., Schellekens A., Scheres A., Schoeman R., Schweitzer J.B., Shah H., Solanto M.V., Sonuga-Barke E., Soutullo C., Steinhausen H.-C., Swanson J.M., Thapar A., Tripp G., Glind G., Brink W., Oord S., Venter A., Vitiello B., Walitza S., Wang Y. (2021) The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder. Neurosci. Biobehav. Rev., 128, 789-818. CrossRef Scholar google search
Posner J., Polanczyk G.V., Sonuga-Barke E. (2020) Attention-deficit hyperactivity disorder. The Lancet, 395(10222), 1-13. CrossRef Scholar google search
Kovalev G.I., Sukhorukova N.A., Kondrakhin E.A., Vasil’eva E.V., Salimov R.M. (2021) Influence of piracetame on the brain receptor systems in CD-1 mice with different attention stability phenotypes. Pharmaceutical Chemistry Journal, 55(8), 10-14. CrossRef Scholar google search
Kovalev G.I., Sukhorukova N.A., Vasil’eva E.V., Kondrakhin E.A., Salimov R.M. (2021) Pantogam and atomoxetine influence on attention stability and distribution of dopamine D2 and GABAB receptors in attention deficit mouse model. Biomeditsinskaya Khimiya, 67(5), 402-410. CrossRef Scholar google search
Kovalev G.I., Sukhorukova N.A., Vasil’eva E.V., Kondrakhin E.A., Salimov R.M. (2021) Analysis of behavioral and neuroreceptor effects of atomoxetine and phenibut in CD-1 subpopulations diverging in sustained attention. Russian Journal of Experimental and Clinical Pharmacology, 84(4), 3-11. CrossRef Scholar google search
Kovalev G.I., Sukhorukova N.A., Kondrakhin E.A., Vasil’eva E.V., Salimov R.M. (2021) Subchronic administration of semax increases attention stability in CD-1 mice via modulation D2-dopamine receptors in the prefrontal cortex. Russian Journal of Experimental and Clinical Pharmacology, 84(6), 3-10. CrossRef Scholar google search
Kovalev I.G., Voronina T.A., Litvinova S.A., Zhmurenko L.A., Mokrov G.V. (2017) Comparison of the anticonvulsant and mnemotropic properties of new derivatives of 4-phenylpyrrolidone, levetiracetam and piracetam, in outbred mice and rats. Russian Journal of Experimental and Clinical Pharmacology, 80(6), 13-18. CrossRef Scholar google search
Salimov R.M., Kovalev G.I. (2013) Effect of atomoxetine on behavior of outbred mice in the enrichment discrimination test. J. Behav. Brain Sci., 3(2), 210-216. CrossRef Scholar google search
Kovalev G.I., Salimov R.M., Sukhorukova N.A., Kondrakhin E.A., Vasileva E.V. (2020) Neuroreceptor profile and behavior of CD-1 mice subpopulations with different attention stability. Neurochemical Journal, 37(1), 1-9. CrossRef Scholar google search
Iversen L.L., Glowinski J. (1966) Regional studies of catecholamines in the rat brain. II. Rate of turnover of catecholamines in various brain regions. J. Neurochemistry, 13(8), 671-682. CrossRef Scholar google search
Breese C.R., Marks M.J., Logel J., Adams C.E., Sullivan B., Collins A.C., Leonard S. (1997) Effect of smoking history on [3H]nicotine binding in human postmortem brain. J. Pharmacol. Exp. Ther., 282(1), 7-13. Scholar google search
Sun W., Ginovart N., Ko F., Seeman P., Kapur S. (2003) In vivo evidence for dopamine-mediated internalization of D2-receptors after amphetamine: Differential findings with [3H]raclopride versus. CrossRef Scholar google search
Bowery N.G., Hill D.R., Hudson A.L. (1985) [3H](-)Baclofen: improved ligand for GABAB sites. Neuropharmacology, 24(3), 207-210. CrossRef Scholar google search
Szekely A.M., Barbaccia M.L., Costa E. (1987) Effect of a protracted antidepressant treatment on signal transduction and [3H](-)-baclofen binding at GABAB receptors. J. Pharmacol. Exp. Ther., 243(1), 155-159. Scholar google search
Waterborg J.H., Matthews H.R. (1984) The Lowry method for protein quantitation. Methods Mol. Biol., 1, 1-3. CrossRef Scholar google search
Kudrin V.S., Miroshnichenko I.I., Rayevsky K.S. (1988) Difference in the mechanism of the autoreceptor regulation of dopamine release and biosynthesis in rat brain subcortical regions. Neurochemical Journal, 7(1), 3-10. Scholar google search
Kovalev I.G., Vasileva E.V., Bokov R.O., Salimov R.M., Kovalev G.I. (2017) Effects of levetiracetam and a new derivative of 4-phenylpyrrolidone GIZh-290 in a closed cross maze in BALB/c and C57BL/6 mice. Farmakokinetika i Farmakodinamika, 2, 25-29. Scholar google search
Kovalev I.G., Vasileva E.V., Kondrakhin E.A., Voronina T.A., Kovalev G.I. (2017) The role of glutamate and GABA receptors in the anticonvulsive effects of levetiracetam and a 4-phenylpyrrolidone derivative (GIZh-290) in rats. Neurochemical Journal, 34(4), 335-343. CrossRef Scholar google search
Verrotti A., Moavero R., Panzarino G., di Paolantonio C., Rizzo R., Curatolo P. (2018) The challenge of pharmacotherapy in children and adolescents with epilepsy-ADHD comorbidity. Clin. Drug. Investig., 38(1), 1-8. CrossRef Scholar google search
Jensen V., Rinholm J.E., Johansen T.J., Medin T., Storm-Mathisen J., Sagvolden T., Hvalby O. et al. (2009) N-methyl-D-aspartate receptor subunit dysfunction at hippocampal glutamatergic synapses in an animal model of attention-deficit/hyperactivity disorder. Neuroscience, 158(1), 353-364. CrossRef Scholar google search
Howells F.M., Russell V.A. (2008) Glutamate-stimulated release of norepinephrine in hippocampal slices of animal models of attention-deficit/hyperactivity disorder (spontaneously hypertensive rat) and depression/anxiety-like behaviours (Wistar-Kyoto rat). Brain Res., 1200, 107-115. CrossRef Scholar google search
Gilby K.L. (2008) A new rat model for vulnerability to epilepsy and autism spectrum disorders. Epilepsia, 49(Suppl. 8), 108-110. CrossRef Scholar google search
Selemon L.D. (2014) Frontal lobe synaptic plasticity in development and disease: modulation by the dopamine D1 receptor. Curr. Pharm. Des., 20(32), 5194-5201. CrossRef Scholar google search
