[The original novel nootropic and neuroprotective agent noopept].
The paper describes pharmacological properties of the new nootropic drug noopept created using an original approach based on the imitation of a nonpeptide nootrope structure by means of the short-peptide design. In particular, the structure of pyracetam was designed using dipeptide nootropes. Experimental investigations of noopept (N-phenylacetyl-L-polyglycine ethyl ester) showed that the new drug exceeds pyracetam both with respect to the effective dose level (1000 times lower for noopept than for pyracetam) and in the spectrum of mnemotropic activity. In contrast to pyracetam facilitating only the early stages of the memory process, noopept positively influences the memory consolidation and retrieval steps as well. The new drug produces an additional selective anxiolytic action. The pronounced neuroprotective effect of noopept was demonstrated both in vivo (in cases of various forms of brain ischemia) and in vitro (on various neuronal models). The drug action is based on the antioxidant effect, the antiinflammatory action, and the ability to inhibit the neurotoxicity of excess calcium and glutamate, and to improve the blood rheology. It was established for the first time that the activity of noopept is retained both upon parenteral introduction and upon peroral administration, which is a principal advantage of this proline-containing dipeptide over other, more complex peptides. This property provided a basis for the development of a medicinal form of noopept for peroral usage. At present, noopept tablets (noopept 5 and 10 mg) are under clinical assessment as a means of treating cognitive deficiency of cerebrovascular and post-traumatic origin.
Ostrovskaia
R U
RU
Laboratory of Psychopharmacology, Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya ul. 8, Moscow, 125315 Russia.
Gudasheva
T A
TA
Voronina
T A
TA
Seredenin
S B
SB
D000818:Animals; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D010889:Piracetam / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D004151:Dipeptides; D018696:Neuroprotective Agents; D018697:Nootropic Agents; C103871:ethyl phenylacetyl-Pro-Gly; D010889:Piracetam