Pro-Cognitive Effects of Non-Peptide Analogues of Soluble Amyloid Peptide Precursor Fragment sAPP.

We studied pro-cognitive effect of two heterocyclic low-molecular-weight compounds that serve as non-peptide analogues of soluble fragment of amyloid peptide precursor (sAPP). Intracerebroventricular and systemic administration of peptide mimetics P2 and P5 improved weak memory on the model of passive avoidance in chicks and in the object location task in mice. Both compounds were effective if administered close to the moment of training or 4 h after it.

[Simultaneous AMPA receptor potentiation and NMDA receptor blockade as strategy for creating effective stimulants for cognitive functions].

New compounds representing derivatives of acyclic isothioureas have been synthesized, which are capable of simultaneously activating AMPA receptors and blocking NMDA receptors. In order to produce cognitive-stimulating effect, of principal importance is the pathway of NMDA receptor blockade produced by the drug. Positive influence is due to the blockade of NMDA receptors either by mechanism of rapid dissociation of intrachannel site or by inhibition of NR2B subunit of NMDA receptor.

[Influence of derivatives of arachidonic and docosohexaenic acids on AMPA receptors in Purkinje neurons and cognitive functions in mice].

The effect of derivatives of arachidonic and docosahexaenoic acids on AMPA receptors in Purkinje cells from the rat cerebellum was studied using the patch-clamp electrophysiological method. It was shown that derivatives of arachidonic acid-arachidonoyl dopamine and docosahexaenoic acid-docosahexaenoyl dopamine and ester of docosahexaenoic acid with ethylene glycol in nanomolar concentrations effectively potentiated the ionic currents caused by activation of AMPA receptors of kainic acid. Ester of docosahexaenoic acid with nitroethylene glycol blocked AMPA receptors, and anandamide (ethanolamide of arachidonic acid) was not effective.

Effects of 17 beta-estradiol and its isomer 17 alpha-estradiol on learning in rats with chronic cholinergic deficiency in the brain.

It was shown for the first time that estrogens 17 beta- and 17 alpha-estradiols compensate impaired cognitive functions in rats with partial chronic deprivation of cholinergic functions in the central nervous system induced by intracerebral administration of selective cholinergic neurotoxin AF64A. 17 beta-Estradiol produced strong dose-dependent changes in the weights of hormone-sensitive endocrine glands, while 17 alpha-estradiol did not affect the weight of the gonads and slightly influenced (in high concentration) the weights of the adrenal glands and thymus. The positive effects of exogenous 17 beta- and 17 alpha-estradiols on cognitive functions are due to their antioxidant properties, rather than due to specific action on hormone-sensitive endocrine glands.

N-acetylserotonin, melatonin and their derivatives improve cognition and protect against beta-amyloid-induced neurotoxicity.

After a single injection of cholinergic neurotoxin ethylcholine aziridinium (AF64A, 3 nmol intracerebroventricularly (i.c.v.