Ostrovskaya R U, Belnik A P, Storozheva Z I
Laboratory of Psychopharmacology, V. V. Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia.
Bull Exp Biol Med. 2008 Jul;146(1):77-80. doi: 10.1007/s10517-008-0211-6.
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).
对成年Wistar大鼠的实验表明，向Meynert基底核注射β-淀粉样蛋白25-35（2微克）会导致长期记忆缺陷，在注射后24天通过条件性被动回避反射（CPAR）中的记忆痕迹检索检测到这种缺陷。研究了一种新型促智和神经保护二肽诺肽对这种认知缺陷严重程度的影响。预防性（在损伤前7天）腹腔注射剂量为0.5毫克/千克的诺肽在该模型条件下完全预防了记忆障碍。如果在损伤后15天开始治疗，此时基底核、皮质和海马体中的神经退行性变化仍然非常明显，诺肽表现出显著的正常化作用。研究了该药物这种作用的机制，除了胆碱阳性作用外，还包括其多组分神经保护作用以及刺激针对β-淀粉样蛋白25-35的抗体产生。诺肽在许多阿尔茨海默病模型中的有效性、高生物利用度和低毒性表明，这种二肽可作为治疗这种疾病（初始和中度阶段）的潜在药物进行进一步研究。
