Piracetam was the first of the 2-oxopyrrolidine (pyrrolidone) chemical family which has been the focus of studies and inquiries for over three decades. It was the result of Corneliu Giurgea’s ground-breaking research on the late 1960s. Giurgea was the one who coined the word “nootropic” (nous + trepein) which means enhancement of memory and learning. This particular term is sometimes associated to other functions including “neuroprotection”.
The clinical studies and trials performed on its discovery were initially concerned of its supposed nootropic effects. From herein, the possibility of neuroprotection immediately after a stroke as well as its use as an antiepileptic agent began. Just recently, interest on piracetam as a nootropic agent rekindled for it was licensed because of its antimyoclonic properties and effects after a mild cognitive injury and stroke. This license however, excluded US FDA. Nevertheless, this restoration of attention was radical as it would likely lead to increased numbers of pyrollidone chemicals entering clinical practice for the next years .
The structure of piracetam has structural similarities with levetiracitam. It has a 5 carbon oxo-pyrrolidone ring also known as racetams which it shares to other nootropic agents . Both piracetam and levetiracetam are pyrrolidone derivatives with comparable chemical structures. This likeness ended on its structural properties as their medical or experimental uses and pharmacological outline are distinctive .
[msgbox]IUPAC/Chemical name: 2-oxo-pyrrolidine acetamide
Chemical property: White solid
Usage: Nootropic agent
Materials (raw): 2-pyrrolidinone, ethyl chloroacetate, methyl chloroacetate and sodium methanolate[/msgbox]
Mechanism of action
The mechanism of action of piracetam and its derivatives remain to be a mystery . Nevertheless, various hypotheses were given out by experts. One of the identified possible mechanisms of action of this particular nootropic agent is the membrane theory.
Piracetam, a cyclic derivative of gamma aminobutyric acid (GABA) is a nootropic agent that acts on the cognitive function without resulting to stimulation or sedation. Though it is related to GABA, it would seem that its mode of action is unconnected to the properties and characteristics of this neurotransmitter. Nevertheless, an increasing amount of evidence reveals that its fundamental effect is strongly associated to the restoration of cell membrane fluidity.
On various researches, it was revealed that piracetam molecules may partially prevent changes on the layers of the membrane. As a consequence, drug-lipid complexes are assumed to cause lipid reorganization which in turn may influence the fluidity and functioning of membranes. Other studies also revealed that piracetam increases fluidity of the membrane particularly when there is abnormal fluidity which is frequently seen on aging.
Restoration of membrane fluidity may then lead to restored neurotransmission, enhanced neuroplasticity, neuroprotection, decreased vasospasm, and reduced erythrocyte adhesion to cell wall which will consequently lead to enhanced neuronal function and microcircuilation .
Other than the membrane theory, its effects on glutamate neurotransmission have been methodically explained. According to experts, it improves the efficacy of the AMPA receptor leading to the improved excitability of neurons. Additionally, piracetam may help enhance the function of acetylcholine through the muscarinic cholinergic receptors which is highly associated to memory development .
Benefits of piracetam
One of the benefits of piracetam include its effectiveness on improving activated blood flow as well as its ability to help in facilitating rehabilitation to aphasic patients. On a prospective study of post-stroke individuals diagnosed with aphasia, piracetam combined with speech therapy leads to the improvement of six language functions compared to three functions with speech therapy alone. This effect is accompanied by a considerable improvement of flow activation on expressive areas of the brain’s left hemisphere .
Apoptosis and oxidative damage prevention
Studies regarding the use of piracetam often cite its effectiveness on a host of neurological disorders. One of these neurological disorders includes Down’s syndrome which was proven in a study undertaken on 2003. On this particular research, it was revealed that piracetam use can help in neuroprotection. Piracetam is said to inhibit damage to the neurons from lipid peroxidation and free radicals accumulation. Its ability to inhibit oxidative stress enables neuroprotection whilst prevent degeneration and neuronal apoptosis to individuals with Down’s syndrome, mental retardation or aging .
Numerous researches were already performed to prove the effectiveness of piracetam as an Alzheimer’s disease (AD) treatment. However, there is no concrete evidence yet that it can treat and replace the primary drugs prescribed for individuals diagnosed with Alzheimer’s. One of these particular studies includes the use of high doses of piracetam for a long period of time.
This study showed that piracetam can help improve remote and recent memory as well as picture series recall. Even with these effects, there were no significant improvements on patients with probable AD after piracetam use. In the end, the researchers simply hypothesized that long term use of piracetam may help in decreasing the progression of cognitive deterioration amongst AD patients .
On other countries like Japan, piracetam is well-known for its ability to treat myoclonus. In fact, on a particular study, it was found out that use of this nootropic agent is effective on myoclonus with emphasis on the cortical type. Not only does it help in myoclonus treatment, it can also help improve convulsions, gait ataxia, handwriting and feeding. It also has the potential ability to enhance psychological well-being including attention deficit, decreased motivation, depression, and sleep disturbances .
Depression and anxiety improvement
Piracetam is also known for its capability of improving depression and anxiety. This was evident on a clinical trial performed early on individuals diagnosed with schizophrenia and depression. In this study, it was found out that rapid clinical enhancement was evident on schizophrenic and depressed (drug resistant) individuals whilst the increase of ATP levels , .
Acute ischemic stroke rehabilitation
The neuroprotective capabilities of piracetam in conjunction with its antithrombotic effects provided the underlying principle of its role on acute ischemic stroke rehabilitation. On a pilot study undertaken to uncover its effects, it was revealed that the use of piracetam is likely to be very effective if it was given early on the onset of acute ischemic stroke (7 hours after onset)especially to post stroke patients suffering with moderate to severe degree effects .
The experimental studies done to reveal the effects and benefits of piracetam are wide ranging with conflicting and controversial results. Hence, it is inadequate to warrant its clinical use on the US. Nevertheless, this insufficiency only justifies the need for further research focusing on the effects and safe use of this nootropic agent.
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