Effect of nooglutil on benzodiazepine withdrawal syndrome and binding of 3H-spiperone with D2 receptors in rat striatum.
A new nootropic preparation nooglutil (N-(5-oxynicotinoyl)-L-glutamic acid), a positive modulator of AMPA receptors for glutamate, administered intraperitoneally in a dose of 70 mg/kg reduced anxiety of rats in the Vogel conflict test after 24-h withdrawal from chronic diazepam treatment (4 mg/kg intraperitoneally for 45 days). Nooglutil (5 nM-750 microM) had no effect on in vitro binding of (3)H-spiperone in intact rats. Systemic administration of 50 mg/kg nooglutil in vivo increased the dissociation constant and density of D(2)receptors. Increasing the dose to 100 mg/kg abolished this effect. Our findings suggest that nooglutil produces an indirect effect on the brain dopaminergic system under normal and pathological conditions and this effect is probably mediated via the glutamatergic system.
Voronina
T A
TA
Laboratory of Psychopharmacology, Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow.
Borlikova
G G
GG
Garibova
T L
TL
Proskuryakova
T V
TV
Petrichenko
O B
OB
Burd
S G
SG
Avakyan
G N
GN
D000818:Animals; D014151:Anti-Anxiety Agents / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D003975:Diazepam / Q000633:toxicity; D005971:Glutamates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009539:Nicotinic Acids / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D005971:Glutamates; D009539:Nicotinic Acids; D018697:Nootropic Agents; D018091:Receptors, AMPA; D017448:Receptors, Dopamine D2; C066295:nooglutil; D013134:Spiperone; D003975:Diazepam