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.
Izucheny povedencheskie i neĭrokhimicheskie éffekty novogo proizvodnogo ratsetama GIZh-290 na modeli defitsita vnimaniia u autbrednykh mysheĭ SD-1. V rezul'tate subkhronicheskogo vvedeniia GIZh-290 (1 mg/kg, 3 mg/kg i 5 mg/kg vnutribriushinno 1 raz v sutki v techenie 6 dneĭ) iskhodno nizkiĭ uroven' vnimaniia u zhivotnykh subpopuliatsii ED-Low, otobrannykh pri predvaritel'nom povedencheskom tipirovanii v teste “zakrytyĭ obogashchennyĭ krestoobraznyĭ labirint” (ZOKL), uvelichivalsia s naibol'sheĭ izbiratel'nost'iu pri vvedenii GIZh-290 v doze 3 mg/kg. Metodom radioligandnogo analiza pokazano, chto v étoĭ doze preparat izmenial v prefrontal'noĭ kore (PFK) mozga zhivotnykh subpopuliatsii ED-Low plotnost' (Bmax) markernykh D2-dofaminovykh i GAMKB-retseptorov do velichin Vmax v subpopuliatsii sravneniia ED-High. Pri étom po dannym VÉZhKh-ÉD v PFK gryzunov ED-Low, poluchavshikh GIZh-290 v doze 3 mg/kg, proiskhodit normalizatsiia tkanevoĭ kontsentratsii kak samogo dofamina (DA), tak i pokazateleĭ ego vnutri- i vnekletochnogo metabolizma (DOFUK/DA i GVK/DA). Poluchennye rezul'taty ukazyvaiut na éffektivnost' izuchaemogo preparata v farmakoterapii defitsita vnimaniia pri ego éksperimental'nom modelirovanii i vozdeĭstvii na potentsial'nye molekuliarnye misheni, vyiavlennye v provedennom issledovanii.
Keywords: D2-receptor; GABAB-receptor; GIZh-290; HPLC-ED; attention deficit.