Noopept efficiency in experimental Alzheimer disease (cognitive deficiency caused by β-amyloid25–35 injection into Meynert basal nuclei of rats)

Abstract

Experiments on adult Wistar rats showed that injection of beta-amyloid25-35 (2 microg) into Meynert basal nuclei caused long-term memory deficiency which was detected 24 days after this injection by the memory trace retrieval in conditioned passive avoidance reflex (CPAR). The effects of noopept, an original nootropic and neuroprotective dipeptide, on the severity of this cognitive deficiency were studied. Preventive (for 7 days before the injury) intraperitoneal injections of noopept in a dose of 0.5 mg/kg completely prevented mnestic disorders under conditions of this model. Noopept exhibited a significant normalizing effect, if the treatment was started 15 days after the injury, when neurodegenerative changes in the basal nuclei, cortex, and hippocampus were still acutely pronounced. The mechanisms of this effect of the drug are studied, including, in addition to the choline-positive effect, its multicomponent neuroprotective effect and stimulation of production of antibodies to beta-amyloid25-35. Noopept efficiency in many models of Alzheimer disease, its high bioavailability and low toxicity suggest this dipeptide for further studies as a potential agent for the treatment of this condition (initial and moderate phases).

Novel Technologies for Dipeptide Drugs Design and their Implantation

“…Noopept showed effectiveness in several animal models of Alzheimer’s disease: olfactory bulbectomy [27], administration of amyloid into Meinert nucleus [28] and intracerebroventricular administration of diabetogenic toxin streptozotocin [29]. Noopept was shown to ameliorate the behavioral consequences of photochemically induced stroke [30] and mechanical trauma of prefrontal cortex [31].…”

Research progress of natural products and their derivatives against Alzheimer’s disease

“…Some researchers believe that the central cholinergic hypothesis is the most relevant to the pathogenesis of AD. The nucleus basalis of Meynert in the basal forebrain of patients with AD is severely damaged 3 , and the content of choline is significantly increased. Severe depletion of presynaptic acetylcholine leads to severe memory loss, therefore, cholinergic agonists and cholinesterase inhibitors are consider for ameliorating cognitive deficits 4 ; Others that tubulin and Aβ cascades work together leading to a series of pathological changes.…”

Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation

“…Compared to piracetam noopept produces a cognition enhancing effect at much lower concentrations and demonstrates activity over a wider range of cognition disturbances and neuronal damages [ 17 ]. Noopept showed effectiveness in several animal models of AD: olfactory bulbectomy [ 18 ], administration of amyloid into Meinert nucleus [ 19 ] and intracerebroventricul administration of diabetogenic toxin streptozotocine [ 20 ]. Moreover, the experimental data on cognitive improving effect of noopept have been confirmed in clinic (Phase III and postregistration trials) demonstrating beneficial effect on cognitive functions in patients with MCI of cerebro-vascular or posttraumatic origin [ 21 ], and in particular in patients with amnestic form of MCI carrying APOE ε 4 + allele [ 22 ].…”