title: [The absence of tolerance and withdrawal syndrome after the treatment with the new L-tryptophane-containing dipeptide anxiolytic GB-115].
abstract: Effects of GB-115, an anxiolytic L-triptophan-containing dipeptide, based on the endogenous tetrapeptide cholecystokinin, were evaluated during and after withdrawal of its long-term administration to rats in comparison with diazepam. It was shown using the "elevated plus-maze" test (EPM) that GB-115 retained its anxiolytic properties after i/p injections at a daily dose of 0.1 mg/kg fo r 30-days. Discontinuation of dipeptide administration 24h and 48 hours after the onset of the experiment did not lead to behavioral (increased anxiety, aggression) and convulsive (decreased corazol sensitivity) manifestations of withdrawal syndrome. In contrast, the withdrawal ofdiazepam (4.0 mg/kg/day, ip, 30 days) induced the anxiogenic response in EPM, reduction of the aggression threshold, and enhancement of convulsive readiness. Significant differences between GB-115 and diazepam effects on the levels of dopamine, norepinephrine, and their metabolites after chronic administration and withdrawal were restricted to striatum.
authors: L G
authors: LG
authors: Kolik
authors: T L
authors: TL
authors: Garibova
authors: S A
authors: SA
authors: Litvinova
authors: A L
authors: AL
authors: Kuznetsova
authors: I G
authors: IG
authors: Kapitsa
authors: I A
authors: IA
authors: Kadnikov
authors: M A
authors: MA
authors: Konstantinopol'skiĭ
authors: T A
authors: TA
authors: Gudasheva
authors: T A
authors: TA
authors: Voronina
authors: S B
authors: SB
authors: Seredenin
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003975:Diazepam / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004151:Dipeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004298:Dopamine / Q000378:metabolism; D004361:Drug Tolerance; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D013375:Substance Withdrawal Syndrome; D013758:Tetragastrin / Q000378:metabolism; D013995:Time
chemical_list: D014151:Anti-Anxiety Agents; D004151:Dipeptides; C520797:GB-115; D013758:Tetragastrin; D003975:Diazepam; D004298:Dopamine; D009638:Norepinephrine