[Multicomponent antithrombotic effect of the neuroprotective prolyl dipeptide GVS-111 and its major metabolite cyclo-L-prolylglycine].
The experiments in vivo showed that the new nootropic prolyl-containing GVS-111 produces an antithrombotic effect, influencing various stages of the blood coagulation process. GVS-111 exhibits anticoagulant and fibrinolytic properties and enhances fibrin destabilization by reducing the XIIIa factor activity. These effects are manifested upon both intraperitoneal (1 mg/kg) and peroral (10 mg/kg) administration of GVS-111 (in both cases, a single daily treatment over a period of 10 days). The same effects (anticoagulant, fibrinolytic, antifibrin-stabilizing) were observed in in vitro experiments with both GVS-111 (10(-3)-10(-6) M) and its main metabolite cyclo-L-prolylglycine (up to 10(-10) M). In addition, the latter metabolite exhibited an antiaggregant effect. The antithrombotic activity of GVS-111, together with previously established neuroprotector properties, low toxicity, and the absence of complications, makes this compound a promising antistroke drug.
Ostrovskaia
R U
RU
Laboratory of Psychopharmacology, Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya ul. 8, Moscow, 125315 Russia.
Liapina
L A
LA
Pastorova
V E
VE
Mirzoev
T Kh
TKh
Gudasheva
T A
TA
Seredenin
S B
SB
Ashmarin
I P
IP
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D026122:Factor XIIIa / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000925:Anticoagulants; D004151:Dipeptides; D005343:Fibrinolytic Agents; D018696:Neuroprotective Agents; D010456:Peptides, Cyclic; D010975:Platelet Aggregation Inhibitors; C103871:ethyl phenylacetyl-Pro-Gly; D005337:Fibrin; C062238:cyclo(prolylglycyl); D026122:Factor XIIIa; D005998:Glycine