Therapeutic Utility of Phosphodiesterase Type I Inhibitors in Neurological Conditions

Abstract

Neuronal plasticity is an essential property of the brain that is impaired in different neurological conditions. Phosphodiesterase type 1 (PDE1) inhibitors can enhance levels of the second messengers cAMP/cGMP leading to the expression of neuronal plasticity-related genes, neurotrophic factors, and neuroprotective molecules. These neuronal plasticity enhancement properties make PDE1 inhibitors good candidates as therapeutic agents in many neurological conditions. However, the lack of specificity of the drugs currently available poses a challenge to the systematic evaluation of the beneficial effect of these agents. The development of more specific drugs may pave the way for the use of PDE1 inhibitors as therapeutic agents in cases of neurodevelopmental conditions such as fetal alcohol spectrum disorders and in degenerative disorders such as Alzheimer's and Parkinson's.

Synthesis of glycosides of resveratrol, pterostilbene, and piceatannol, and their anti-oxidant, anti-allergic, and neuroprotective activities

“…BIOMOL Green, which is used for calculation of the amount of phosphate released, was purchased from Funakoshi Co. PDE activity was measured using a cyclic nucleotide PDE assay kit from Enzo Life Sciences (BML-AK800) according to the manufacturer's instructions, except that PDE 100 mU per well were used. [24][25][26] Stock solutions of inhibitors were prepared as 100 mM in DMSO and diluted to the appropriate concentrations. In the assay, 1 μL of each inhibitor solution was added before the addition of PDE enzyme solution.…”

Is There Treatment Effect of Vinpocetine on Autonomic Dysfunction in Rats With Alzheimer

“…Most studies performed in animal models used doses between 10 and 20 mg/kg [14,15]. These doses translated to humans would result in approximately 1,000 mg, which would be roughly a 20-fold increase in the current doses used in clinicaltrials [16][17][18].…”

Кавинтон (Винпоцетин): Новые Возможности Клинического Применения

“…Âîçìîaeíî, ÷òî âèíïîöåòèí, óâåëè÷èâàÿ óðî-âåíü öÀÌÔ/öÃÌÔ, ñïîñîáñòâóåò ôîñôîðèëèðîâàíèþ ðåöåïòîðîâ ÀÌÐÀ (a-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid) êîòîðûå ìîãóò äâèãàòüñÿ â-è èç ñèíàïòè÷åñêîé ìåìáðàíû, ñîçäàâàÿ, òàêèì îáðàçîì, óñëîâèÿ äëÿ ïîâûøåíèÿ ôóíêöèîíàëüíîé àêòèâíîñòè ðåöåïòîðîâ NMDA (N-methyl-D-aspartate). Âîçíèêàåò äåïîëÿðèçöèÿ ïîñòñèíàïòè÷åñîé ìåìáðàíû, ïðèâîäÿ-ùàÿ ê îñâîáîaeäåíèþ ðåöåïòîðîâ NMDA îò áëîêèðóþ-ùåãî äåéñòâèÿ Mg 2+ , ÷òî îáóñëîâëèâàåò âîçðàñòàíèå ñèíàïòè÷åñêîé àêòèâíîñòè [44]. Ñóùåñòâóþò óáåäè-òåëüíûå äîêàçàòåëüñòâà ñïîñîáíîñòè âèíïîöåòèíà âîññòàíàâëèâàòü íåéðîïëàñòè÷íîñòü, îñëàáëåííóþ ïðè ôåòàëüíîì àëêîãîëüíîì ñèíäðîìå ó ìûøåé [45,21,35].…”