title: The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine.
abstract: The metabolism of a new piracetam analogue, the dipeptide cognitive enhancer N-phenylacetyl-L-prolylglycine ethyl ester (GVS-111) was studied in vivo. GVS-111 itself was not found in rat brain 1 h after 5 mg/kg i.p. administration up to limit of detection (LOD) under high performance liquid chromatography (HPLC) conditions. Three substances corresponding to the three possible GVS-111 metabolites, namely phenylacetic acid, prolylglycine and cyclo-prolylglycine, were found in experimental rat brain samples as well as in controls using HPLC, gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) methods. Only cyclo-prolylglycine concentration increased (2.5-fold) 1 h after GVS-111 administration. Cyclo-prolylglycine formation from GVS-111 in the presence of plasma and brain enzymes was shown in vitro. These data could be considered as evidence that GVS-111 is prodrug which converts in the body to cyclo-prolylglycine, and which is identical to the endogenous cyclopeptide that produces the nootropic activity.
authors.affiliation: Institute of Pharmacology, Russian Academy of Medical Science, Moscow, Russia.
authors.forename: T A
authors.initials: TA
authors.lastname: Gudasheva
authors.forename: S S
authors.initials: SS
authors.lastname: Boyko
authors.forename: R U
authors.initials: RU
authors.lastname: Ostrovskaya
authors.forename: T A
authors.initials: TA
authors.lastname: Voronina
authors.forename: V K
authors.initials: VK
authors.lastname: Akparov
authors.forename: S S
authors.initials: SS
authors.lastname: Trofimov
authors.forename: G G
authors.initials: GG
authors.lastname: Rozantsev
authors.forename: A P
authors.initials: AP
authors.lastname: Skoldinov
authors.forename: V P
authors.initials: VP
authors.lastname: Zherdev
authors.forename: S B
authors.initials: SB
authors.lastname: Seredenin
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004151:Dipeptides / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism; D018697:Nootropic Agents / Q000737:chemistry / Q000378:metabolism*; D010889:Piracetam / Q000494:pharmacology; D051381:Rats
chemical_list: D004151:Dipeptides; D009479:Neuropeptides; D018697:Nootropic Agents; C057749:prolylglycine; C103871:ethyl phenylacetyl-Pro-Gly; D010889:Piracetam