Piracetam - NutraHacker Journal Club
Origins and Overview
Piracetam (2-oxo-1-pyrrolidine acetamide) is a derivative of the neurotransmitter GABA and has a significant impact on various physiological systems. Piracetam was first synthetised by the Romanian chemist Corneliu E. Giurgea during the period between 1950 and 1964. The chemical formula for piracetam is C6H10N2O2 and the elimination half-life is roughly 4-5 hours.
Piracetam has neuronal and vascular effects, the primary of which it restoring cell membrane fluidity, and has shown scientifically to yield improvements in cognitive disorders, cortical myoclonus, dyslexia, pain, hypoxia, and even Sickle Cell Anemia.
Piracetem acts principally on two internal systems, the NMDA (N-methyl-D-aspartate) and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, both glutamate receptors, and has a diverse range of physiological effects owing primarily to reduced red blood cell adhesion to the vascular endothelium and the facilitation of microcirculation.
Piracetam: a review of pharmacological properties and clinical uses
Piracetam, a derivative of the neurotransmitter gamma-aminobutyric acid (GABA), has a variety of physiological effects that may result, at least in part, from the restoration of cell membrane fluidity. At a neuronal level, piracetam modulates neurotransmission in a range of transmitter systems (including cholinergic and glutamatergic), has neuroprotective and anticonvulsant properties, and improves neuroplasticity. At a vascular level, it appears to reduce erythrocyte adhesion to vascular endothelium, hinder vasospasm, and facilitate microcirculation. This diverse range of physiological effects is consistent with its use in a range of clinical indications. Its efficacy is documented in cognitive disorders and dementia, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia. While high doses are sometimes necessary, piracetam is well tolerated.
Correspondence (letter to the editor): Positive Experiences With Piracetam
Cognitive deficits after severe illnesses used to be called “unspecified organic or symptomatic mental disorder”. Cognitive deficits after intensive care are included in this definition. In my experience, an older but still very effective medication is piracetam. It facilitates the provision of oxygen and glucose to the brain cells. It can be administered orally (800–1200 mg) in the morning or at midday, or, initially, as an infusion (12 g) in the morning. If administered after 3 pm, it may cause disrupted sleep; (initial) overdosing may cause restlessness. Older women should be advised that piracetam may increase the libido—something that is often unwanted.
Cerebroprotective effect of piracetam in patients undergoing coronary bypass surgery
Reduction of cognitive function is a possible side effect after cardiac surgery using cardiopulmonary bypass. We investigated the cerebroprotective effect of piracetam on cognitive performance in patients undergoing coronary artery bypass surgery under cardiopulmonary bypass. However, the piracetam patients performed significantly better compared to the placebo patients after the operation and had a less decline of overall cognitive function (p<0.0005). Piracetam has a cerebroprotective effect in patients undergoing coronary artery bypass surgery with the use of cardiopulmonary bypass. It reduces an early postoperative substantial decline of neuropsychological abilities.
Pharmacodynamic evaluation of L-carnitine and piracetam in muscle injury induced by the chronic use of simvastatin
To evaluate the effect of L-carnitine and piracetam on the muscle injury induced by simvastatin in healthy male subjects during the therapy with oral doses of 10 mL of a solution containing L-carnitine 100 mg/mL + piracetam 80 mg/mL (test group) or placebo (control group) and 40 mg simvastatin once a day during 35 consecutive days. The effect of L-carnitine and piracetam in the reduction of myopathic symptomatology caused by exercise, as well as safety and tolerability were also evaluated.
Concomitant use of L-carnitine and piracetam might have a muscle-protective effect and protection against simvastatin-induced myalgia. Furthermore, the formulation was safe and well tolerated by the subjects investigated in this trial.
Protective effects of l-carnitine and piracetam against mitochondrial permeability transition and PC3 cell necrosis induced by simvastatin
Mitochondrial oxidative stress followed by membrane permeability transition (MPT) has been considered as a possible mechanism for statins cytotoxicity. Statins use has been associated with reduced risk of cancer incidence, especially prostate cancer. The results provide evidence that simvastatin induced MPT and cell necrosis were sensitive to either l-carnitine or piracetam in a dose-dependent fashion and mediated by additive mechanisms. When combined, l-carnitine and piracetam acted at concentrations significantly lower than they act individually.
Mitochondrial Function, Dynamics, and Permeability Transition: A Complex Love Triangle as A Possible Target for the Treatment of Brain Aging and Alzheimer's Disease
Because of the failure of all amyloid-β directed treatment strategies for Alzheimer's disease (AD), the concept of mitochondrial dysfunction as a major pathomechanism of the cognitive decline in aging and AD has received substantial support. Accordingly, improving mitochondrial function as an alternative strategy for new drug development became of increasing interest and many different compounds have been identified which improve mitochondrial function in preclinical in vitro and in vivo experiments. However, very few if any have been investigated in clinical trials, representing a major drawback of the mitochondria directed drug development. To overcome these problems, we used a top-down approach by investigating several older antidementia drugs with clinical evidence of therapeutic efficacy. These include EGb761® (standardized ginkgo biloba extract), piracetam, and Dimebon. All improve experimentally many aspects of mitochondrial dysfunction including mitochondrial dynamics and also improve cognition and impaired neuronal plasticity, the functionally most relevant consequences of mitochondrial dysfunction. All partially inhibit opening events of the mitochondrial permeability transition pore (mPTP) which previously has mainly been discussed as a mechanism relevant for the induction of apoptosis.
Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function
The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline.
The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide
The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress. Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Abeta(1-42).
Piracetam improves mitochondrial dysfunction following oxidative stress
In conclusion, therapeutically relevant in vitro and in vivo concentrations of piracetam are able to improve mitochondrial dysfunction associated with oxidative stress and/or aging. Mitochondrial stabilization and protection might be an important mechanism to explain many of piracetam's beneficial effects in elderly patients.
Improvement of mitochondrial function and dynamics by the metabolic enhancer piracetam
As a specific feature of piracetam, beneficial effects are usually associated with mitochondrial dysfunction. In previous studies we were able to show that piracetam enhanced ATP production, mitochondrial membrane potential as well as neurite outgrowth in cell and animal models for aging and AD. To investigate further the effects of piracetam on mitochondrial function, especially mitochondrial fission and fusion events, we decided to assess mitochondrial morphology. Human neuroblastoma cells were treated with the drug under normal conditions and under conditions imitating aging and the occurrence of ROS (reactive oxygen species) as well as in stably transfected cells with the human wild-type APP (amyloid precursor protein) gene. This AD model is characterized by expressing only 2-fold more human Aβ (amyloid β-peptide) compared with control cells and therefore representing very early stages of AD when Aβ levels gradually increase over decades. Interestingly, these cells exhibit an impaired mitochondrial function and morphology under baseline conditions. Piracetam is able to restore this impairment and shifts mitochondrial morphology back to elongated forms, whereas there is no effect in control cells.
Preventive effect of piracetam and vinpocetine on hypoxia-reoxygenation induced injury in primary hippocampal culture
Administration of 1mM Piracetam or 500 nM Vinpocetine significantly prevents the culture from hypoxia-reoxygenation injury when determined by Neutral Red assay, LDH release and Acetylcholine esterase activity. Results showed that Piracetam and Vinpocetine supplementation significantly prevented the fall of mitochondrial membrane potential, rise in ROS generation and reduction in antioxidant levels associated with the hypoxia-reoxygenation injury. In conclusion, the present study establishes that both Piracetam and Vinpocetine give neuroprotection against hypoxia-reoxygenation injury in primary hippocampal cell culture.
Oxidative stress in a model of toxic demyelination in rat brain: the effect of piracetam and vinpocetine
GSH increased by the higher dose of piracetam and by vinpocetine which also decreased serum nitric oxide.
Pharmacological protection against hypoxia induced amnesia in rats
Rats treated with Piracetam (UCB 6215) at 100 and 500 mg/kg, were completely protected against “immediate” hypoxia, as judged by their learning performance.
Nootropic drugs and aging
Nootropic drugs (which aid in the plasticity of the CNS) act at the telencephalic level through a series of bioenergetic, hemorheological, microcirculatory, and neurochemical mechanisms. A review of recent data shows a facilitation by piracetam of the efficiency of the central cholinergic system in young and old animals. Piracetam has been found to facilitate learning, memory, and the efficiency of interhemispheric connectivity.
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