Piracetam

Piracetam (brand name: Nootropil®, Myocalm®) is a nootropic. It is a cerebral function regulating drug which, it is claimed, is able to enhance cognition and memory, slow down brain aging, increase blood flow and oxygen to the brain, aid stroke recovery, and improve Alzheimer's, Down's Syndrome, dementia, and dyslexia, among others. Piracetam's chemical name is 2-oxo-1-pyrrolidine acetamide; it shares the same 2-oxo-pyrrolidone base structure with 2-oxo-pyrrolidine carboxylic acid (pyroglutamate). Piracetam is a cyclic derivative of GABA. It is one of the racetams. Though largely ignored in the United States, piracetam is commonly prescribed in Europe for a variety of conditions. However, in some places, due to its non-toxic nature and its general health benefits it is seen more as a food supplement than as a drug. One of its general health effects is said to be toning of damaged nerves and muscles (although this is scientifically unverified). It is safe for use by itself as a non-prescription drug in a reasonably healthy person.

Effects
Several meta-reviews of literature on piracetam indicate that piracetam increases performance on a variety of cognitive tasks among dyslexic children, though this may reflect its enhancement of cross-hemispheric communication and of cognitive function in general, rather than a specific improvement in whatever causes dyslexia. Piracetam also seems to inhibit brain damage caused by a variety of factors including hypoxia and excessive alcohol consumption.

Piracetam has been studied in an extensive number of clinical experiments, and has shown positive results in the treatment of post-stroke aphasia, epilepsy, cognitive decline following heart and brain surgery, dementia, and myoclonus.

Piracetam appears to increase communication between the two hemispheres of the brain, and increases activity of the corpus callosum.

Mechanisms of action
The mechanism of action of piracetam is not known, although it is hypothesized to act on ion channels or ion carriers, thus leading to non-specific increased neuron excitability, while explaining its lack of agonistic or inhibitory effect on synaptic action (quite unlike most neurotransmitters), and its low toxicity. It has been found to increase blood flow and oxygen consumption in parts of the brain.

Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors which are implicated in memory processes. Furthermore, Piracetam may have an effect on NMDA glutamate receptors which are involved with learning and memory processes. Piracetam is thought to increase cell membrane permeability. Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Ca2+, K+). It has been found to increase oxygen consumption in the brain, apparently in connection to ATP metabolism, and increases the activity of adenylate kinase in rat brain. Piracetam appears to increase the synthesis of cytochrome b5, which is a part of the electron transport mechanism in mitochondria. It also increases the permeability of the mitochondria of some intermediaries of the Krebs cycle.

History
Piracetam was first synthesized in 1964 by scientists at the Belgian pharmaceutical company UCB led by Dr Corneliu E. Giurgea. The drug was the first of the so-called nootropics ("smart drugs" or "cognitive enhancers"), that is, substances which purportedly enhance mental performance. The term nootropic was coined by Giurgea. Nootropil was launched clinically by UCB in the early 1970s and remains an important product of that company in Europe.

Approval and usage
Piracetam is primarily used in Europe, Asia, South America and the US. Piracetam is legal to import into the United Kingdom and the United States for personal use with or without prescription as with other prescription-only drugs. As of June of 2006, piracetam is sold in the United States as a dietary supplement. It has become popular as a cognitive enhancement drug among students, who often buy it in bulk as a powder and then consume it with orange juice to mask the strong, bitter taste. A two week regimen of piracetam was found to enhance verbal memory in healthy college students in a double-blind, placebo-controlled study. It is used by parents as a treatment for childhood autism, though no study has yet produced results which would support such a use.

Aging
Piracetam appears to reverse the effects of aging in the brains of mice.

Piracetam appears to reduce levels of lipofuscin in the rat brain. (Lipofuscin accumulation is common symptom of aging and alcoholism).

Alcoholism
Piracetam appears to be effective in treating alcoholism or its symptoms.

Alzheimer's and senile dementia
Piracetam appears to be effective for improving cognition in Alzheimer's disease and senile dementia patients.

Clotting, coagulation, vasospastic disorders
Piracetam is useful as a long term treatment for clotting, coagulation, and vasospastic disorders such as Raynaud's phenomenon and deep vein thrombosis It is an extremely safe anti-thrombotic agent which operates through the novel mechanism of inhibiting platelet aggregation and enhancing blood cell deformability. Because traditional anti-thrombotic drugs operate through the separate mechanism of inhibiting clotting factors, co-adminsitration of piracetam has been shown to highly complement the efficacy and safety of traditional Warfarin/Heparin anti-coagulation therapy. The most effective treatment range for this use is a daily dose of 4.8 to 9.6 grams divided into three daily doses at 8 hours apart. Piracetam is currently being investigated as a complement or alternative to Warfarin as a safe and effective long term treatment for recurring deep vein thrombosis.

Stroke, ischemia and symptoms
Piracetam has been found to improve cognition after stroke, and reduce symptoms, such as aphasia. It also improves cognition in cases of chronic ischemia.

Dyspraxia and Dysgraphia
Due to its supposed effect on nerves and muscles it is sometimes prescribed as an aid to Muscle or dexterity training. There has not been a specific study as to whether it is beneficial in this aspect. Vinpocetine, another purported nootropic with which piracetam is indirectly synergesic, is confirmed to help with these conditons to a certain degree.

Schizophrenia
Piracetam improves cognitive performance of schizophrenics as it does with non-schizophrenics, but does not improve or worsen the chronic schizophrenia disease state.

Dosage
Piracetam is usually supplied in 800 mg tablets or capsules. Some bulk or nutritional suppliers supply it in a powder form. The recommended dosage varies based on the indication, usually ranging from 1.6-9.6 grams daily (2-12 pills daily). Some people report faster results when taking 1-2 pills every hour for 4-6 hours or taking 4-8 pills at once for the first few days to notice an effect.

For blood coagulation, clotting, and vasospastic disorders such as Raynaud's phenomenon or deep vein thrombosis, the most effective treatment range is a daily dose of 4.8 to 9.6 grams divided into three daily doses at 8 hours apart.

It has been studied up to 45 grams daily without major side effects.

It has no known LD-50 in humans when taken orally.

Contraindications
Piracetam is contra-indicated in patients with severe renal impairment (renal creatinine clearance of less than 20 ml per minute), hepatic (liver) impairment and to those under 16 years of age. It is also contraindicated in patients with cerebral haemorrhage and in those with hypersensitivity to piracetam, other pyrrolidone derivatives or any of the excipients.

Special warnings and precautions for use
Due to the effect of piracetam on platelet aggregation, caution is recommended in patients with underlying disorders of haemostasis, major surgery or severe haemorrhage.

Abrupt discontinuation of treatment should be avoided as this may induce myoclonic or generalised seizures in some myoclonic patients.

As piracetam is almost exclusively excreted by the kidneys caution should be exercised in treating patients with known renal impairment. In renally impaired and elderly patients, an increase in terminal half-life is directly related to renal function as measured by creatinine clearance. Dosage adjustment is therefore required in those with mild to moderate renal impairment and elderly patients with diminished renal function.

Side effects
Piracetam has been found to have very few side effects, and those it has are typically "few, mild, and transient." A large-scale, 12-week trial of high-dose piracetam found no adverse effects occurred in the group taking piracetam as compared to the placebo group. Many other studies have likewise found piracetam to be well-tolerated.

Symptoms of general excitability, including anxiety, insomnia, irritability, headache, agitation, nervousness, and tremor - are occasionally reported. . Such symptoms seem more likely reported in connection with caffeine consumption (coffee), or with monosodium glutamate (a common additive in many processed foods). Effects can be reduced with magnesium supplements. Headache from use of piracetam may be alleviated by coadministration of an acetylcholine biosynthetic precursor, or a drug with cholinergic effects, such as choline bitarate, choline citrate, lecithin, cyprodenate or centrophenoxine.