Changes of High-Affinity Choline Uptake in the Hippocampus of Old Rats after Long-Term Administration of Two Nootropic Drugs (Tacrine and <i>Ginkgo biloba </i>Extract)

Abstract

The effect of tacrine (THA), the cholinesterase inhibitor, and Ginkgo biloba extract (EGb) on the sodium-dependent high-affinity choline uptake (HACU) into hippocampal synaptosomes was studies in vivo in model experiments after long-term administration in old rats (THA 5 or 10 mg/kg/day p.o. for 3 months; EGb 50 or 100 mg/kg/day p.o. for 30 days) and in vitro tests. EGb increased HACU both in vivo and in vitro experiments. On the contrary, THA induced a decrease of HACU under both conditions, suggesting a negative impact on the cholinergic neuronal activity.

Influence of the Severity of Cognitive Impairment on the Effect of the <i>Ginkgo biloba</i> Extract EGb 761^® in Alzheimer’s Disease

“…Directly or indirectly related to these effects, EGb decreases lipid peroxidation [19] and protects hippocampal neurons against cell death induced by ß-amyloid [20]. Furthermore, EGb restores receptor density, particularly increasing the number of hippocampal muscarinic acetylcholine [21] and cortical 5-hydroxytryptamine 1A receptors [22], while enhancing high-affinity choline uptake [23]. EGb also protects the energy metabolism of neurons under conditions of oxygen and substrate deficiency [24][25][26] and maintains Na/K-ATPase activity [27], which ensures normal membrane function.…”

Inhibitors of Acetylcholinesterase Derived from 7-Methoxytacrine and Their Effects on the Choline Transporter CHT1

“…The abilities of new derivatives of 7-MEOTA to inhibit HACU levels (I max between 57 and 68%, IC 50 between 2 and 20 µ M ) and [3H]HC-3-specific binding (I max between 26 and 45%, IC 50 between 36 and 95 µ M ) did not markedly differ between each other and were comparable with 7-MEOTA; however, all were slightly more efficient than tacrine (Table 2). Nevertheless, we suppose that the interactions of new AChE inhibitors with CHT1 could be involved in the enhancement of their detrimental side effects and/or in the attenuation of their promising effects, since even a small change (approximately 10%) in HACU levels could influence the synthesis of ACh in the case of long-term administration [20,32]. Incidentally, especially higher doses of AChE inhibitors and a longer duration of continuous treatment can be typically seen in clinical practice [59,60].…”

“…On the other hand, some AChE inhibitors are also able to markedly inhibit the HACU levels. For example, our previous data revealed dose-dependent inhibition of rat hippocampal HACU by tacrine applied in vivo and in vitro [32] or by some oxime reactivators (weak AChE inhibitors) in experiments in vitro [33,34]. Therefore, we suppose that a certain similarity between the ACh binding site of AChE and the choline binding site of CHT1 is probable.…”

Препарати Гінкго Білоба: Шляхом Відкриттів У клінічній Нейрофармакології

“…ЭГ обладает способностью стимулировать обратный захват холина в синаптосомах и повышать плотность М-холинорецепторов в лобной коре и гиппокампе [13,19,21] -регионах мозга, пря-мо связанных с реализацией когнитивных функций. Учитывая, что в основе возрастной когнитивной дис-функции лежит именно ослабление холинергических процессов, прежде всего на уровне обратного захвата и рецепторного связывания ацетилхолина [32], упомя-нутые механизмы действия можно считать фундамен-том давно выявленных геропротекторных свойств ЭГ, направленных на торможение ведущих механизмов старения мозга [4].…”