Piracetam is a drug marketed as a treatment for myoclonus. It is also used as a cognitive enhancer to improve memory, attention, and learning. Evidence to support its use is unclear, with some studies showing modest benefits in specific populations and others showing minimal or no benefit. Piracetam is sold as a medication in many European countries. Sale of piracetam is not illegal in the United States, although it is not regulated nor approved by the FDA so it is legally sold for research use only.
Piracetam is in the racetams group, with chemical name 2-oxo-1-pyrrolidine acetamide. It is a derivative of the neurotransmitter GABA and shares the same 2-oxo-pyrrolidone base structure with pyroglutamic acid. Piracetam is a cyclic derivative of GABA (gamma-aminobutyric acid). Related drugs include the anticonvulsants levetiracetam and brivaracetam, and the putative nootropics aniracetam and phenylpiracetam.
A 2001 Cochrane review concluded that there was not enough evidence to support piracetam for dementia or cognitive problems. A 2005 review found some evidence of benefit in older subjects with cognitive impairment. In 2008, a working group of the British Academy of Medical Sciences noted that many of the trials of piracetam for dementia were flawed.
Some sources suggest that piracetam's overall effect on lowering depression and anxiety is higher than on improving memory. However, depression is reported to be an occasional adverse effect of piracetam.
The LD50 for oral consumption in humans has not been determined. The LD50 is 5.6 g/kg for rats and 20 g/kg for mice, indicating extremely low acute toxicity. For comparison, in rats the LD50 of vitamin C is 12 g/kg and the LD50 of table salt is 3 g/kg.
Mechanisms of action
Piracetam's mechanism of action, as with racetams in general, is not fully understood. The drug influences neuronal and vascular functions and influences cognitive function without acting as a sedative or stimulant. Piracetam is a positive allosteric modulator of the AMPA receptor, although this action is very weak and its clinical effects may not necessarily be mediated by this action. It is hypothesized to act on ion channels or ion carriers, thus leading to increased neuron excitability.GABA brain metabolism and GABA receptors are not affected by piracetam
Piracetam was first made some time between the 1950s and 1964 by Corneliu E. Giurgea. There are reports of it being used for epilepsy in the 1950s.
Society and culture
In 2009 piracetam was reportedly popular as a cognitive enhancement drug among students.
Piracetam is an uncontrolled substance in the United States meaning it is legal to possess without a license or prescription.
In the United States, piracetam is not approved by the Food and Drug Administration. Piracetam is not permitted in compounded drugs or dietary supplements in the United States. Like most research chemicals, it has been available over-the-counter, self-regulated, and third-party lab tested by many US companies for decades.
In the United Kingdom, piracetam is approved as a prescription drug Prescription Only Medicine (POM) number is PL 20636/2524 for adult with myoclonus of cortical origin, irrespective of cause, and should be used in combination with other anti-myoclonic therapies.
In Japan piracetam is approved as a prescription drug.
Piracetam has no DIN in Canada, and thus cannot be sold but can be imported for personal use in Canada.
In Hungary, piracetam was a prescription-only medication, but as of 2020, no prescription is required and piracetam is available as an over-the-counter drug under the name Memoril Mite, and is available in 600 mg pills.
Brivaracetam—an analogue of piracetam with the same additional side chain as levetiracetam and a three–carbon chain. It exhibits greater antiepileptic properties than levetiracetam in animal models, but with a somewhat smaller, although still high, therapeutic range.
Levetiracetam—an analogue of piracetam bearing an additional CH3–CH2– sidechain and bearing antiepileptic pharmacological properties through a poorly understood mechanism probably related to its affinity for the vesicle protein SV2A.
^Müller WE, Koch S, Scheuer K, Rostock A, Bartsch R (January 1997). "Effects of piracetam on membrane fluidity in the aged mouse, rat, and human brain". Biochemical Pharmacology. 53 (2): 135–140. doi:10.1016/s0006-2952(96)00463-7. PMID9037245.
^Farooq MU, Min J, Goshgarian C, Gorelick PB (September 2017). "Pharmacotherapy for Vascular Cognitive Impairment". CNS Drugs (Review). 31 (9): 759–776. doi:10.1007/s40263-017-0459-3. PMID28786085. S2CID23271739. Other medications have been considered or tried for the treatment of VCI or VaD. These include [...] piracetam. There is no convincing evidence about the efficacy of these medications in the treatment of VCI.
^Yeo SH, Lim ZI, Mao J, Yau WP (October 2017). "Effects of Central Nervous System Drugs on Recovery After Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials". Clinical Drug Investigation. 37 (10): 901–928. doi:10.1007/s40261-017-0558-4. PMID28756557. S2CID6520934.
^Chouinard G, Annable L, Ross-Chouinard A, Olivier M, Fontaine F (1983). "Piracetam in elderly psychiatric patients with mild diffuse cerebral impairment". Psychopharmacology. 81 (2): 100–106. doi:10.1007/BF00429000. PMID6415738. S2CID32702769.
^Hakkarainen H, Hakamies L (1978). "Piracetam in the treatment of post-concussional syndrome. A double-blind study". European Neurology. 17 (1): 50–55. doi:10.1159/000114922. PMID342247.
^ abGrau M, Montero JL, Balasch J (1987). "Effect of Piracetam on electrocorticogram and local cerebral glucose utilization in the rat". General Pharmacology. 18 (2): 205–211. doi:10.1016/0306-3623(87)90252-7. PMID3569848.
^Nickolson VJ, Wolthuis OL (October 1976). "Effect of the acquisition-enhancing drug piracetam on rat cerebral energy metabolism. Comparison with naftidrofuryl and methamphetamine". Biochemical Pharmacology. 25 (20): 2241–2244. doi:10.1016/0006-2952(76)90004-6. PMID985556.
^Tacconi MT, Wurtman RJ (1986). "Piracetam: physiological disposition and mechanism of action". Advances in Neurology. 43: 675–685. PMID3946121.
^Yeh HH, Yang YH, Ko JY, Chen SH (July 2006). "Rapid determination of piracetam in human plasma and cerebrospinal fluid by micellar electrokinetic chromatography with sample direct injection". Journal of Chromatography A. 1120 (1–2): 27–34. doi:10.1016/j.chroma.2005.11.071. PMID16343512.
^Bravo-Martínez J, Arenas I, Vivas O, Rebolledo-Antúnez S, Vázquez-García M, Larrazolo A, García DE (October 2012). "A novel CaV2.2 channel inhibition by piracetam in peripheral and central neurons". Experimental Biology and Medicine. 237 (10): 1209–1218. doi:10.1258/ebm.2012.012128. PMID23045722. S2CID25909697.