Clinical use of piracetam in epileptic patients

Chaudhry, H.R.; Najam, Najma; Mahieu, Cédric de; Raza, Asif; Ahmad, Nasir

doi:10.1016/s0011-393x(05)80407-2

Cited by 14 publications

(9 citation statements)

References 6 publications

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“…The AEDs with cognition‐enhancing activity or combination treatment of nootropics and AEDs might offer advantages for antiepileptic therapy. Piracetam has been reported to have positive influence on cognitive functions and to improve seizure protection in epilepsy patients receiving CBZ (57), whereas oxiracetam has been reported to show no meaningful effect on memory function in patients with epilepsy (58). The pharmacologic profile of NEF seems to bring about a benefit for epilepsy patients.…”

Section: Discussionmentioning

confidence: 99%

Anticonvulsant Properties of the Novel Nootropic Agent Nefiracetam in Seizure Models of Mice and Rats

Kitano

Komiyama²,

Makino³

et al. 2005

Epilepsia

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Summary:Purpose: Nefiracetam (NEF) is a novel pyrrolidone-type nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognitionenhancing effects. The present study focused on the anticonvulsant effect of NEF and its potential for antiepileptic therapy.Methods: The anticonvulsant properties of NEF were investigated in experimental seizure models of mice and rats, compared with levetiracetam (LEV) and other standard antiepileptic drugs [AEDs; zonisamide (ZNS), phenytoin (PHT), carbamazepine (CBZ), valproic acid (VPA), diazepam (DZP), and ethosuximide (ESM)]. With reference to standard programs for evaluating potential AEDs, the study included the traditional maximal electroshock seizure and subcutaneous chemoconvulsant (pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate) seizure tests and two threshold models (the increasing-current electroshock seizure test and intravenous pentylenetetrazole seizure threshold test). Neurotoxic activities were examined with the rotarod test and traction test.Results: NEF inhibited electroshock-induced seizures at nontoxic doses, whereas it had no effect on seizures chemically induced by pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate. The anticonvulsant spectrum of NEF paralleled that of ZNS, PHT, and CBZ. The anticonvulsant efficacy of NEF was comparable with that of ZNS and less potent than that of PHT, CBZ, and DZP. However, the safety margin of NEF was superior to that of ZNS, CBZ, VPA, and DZP. LEV showed only slight anticonvulsant effects in threshold models, and it was not effective in conventional screening models.Conclusions: These results suggest that NEF has distinct anticonvulsant spectrum and mechanisms from those of LEV. NEF is an orally active and safe AED, and it possesses a potential for antiepileptic therapy. Key Words: NefiracetamLevetiracetam-Nootropic-Seizure-Antiepileptic.Cognition-enhancing agents (or nootropics) are drugs used for the treatment of impaired brain function resulting from cerebral deficiencies such as senile dementia or cerebral vascular disorders (1-3). Nefiracetam [NEF; N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384] is a novel pyrrolidone-type nootropic and has been reported to enhance learning acquisition and to improve experimentally induced amnesia in various animal models (4-7). Electrophysiologic and neurochemical studies have demonstrated that NEF activates N/L-type Ca 2+ channels (8,9), and cholinergic, monoaminergic and γ -aminobutyric acid (GABA)ergic systems (10-15).Some pyrrolidone derivatives such as piracetam and oxiracetam have been reported to possess anticonvulsant activities (16) or synergistic effects in combination with antiepileptic drugs (AEDs) (17,18). Piracetam has been Accepted February 6, 2005. Address correspondence and reprint requests to Dr. Y. Kitano at New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., 1-16-13 Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan. E-mail: kitanpm...

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Section: Discussionmentioning

confidence: 99%

Anticonvulsant Properties of the Novel Nootropic Agent Nefiracetam in Seizure Models of Mice and Rats

Kitano

Komiyama²,

Makino³

et al. 2005

Epilepsia

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“…Piracetam has been reported not only to lessen cognitive disturbances but also to reduce myoclonic jerks [4,5]. However, in order to be effective in the treatment of myoclonic jerks a very high dose of piracetam (up to 16 g/day or more) is necessary.…”

Section: Introductionmentioning

confidence: 99%

Photosensitive epilepsy: a model to study the effects of antiepileptic drugs. Evaluation of the piracetam analogue, levetiracetam

Trenité

Marescaux

Stodieck³

et al. 1996

Epilepsy Research

162

101

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General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. AbstractThe experimental antiepileptic drug, levetiracetam (UCB L059), a piracetam analogue has been investigated in photosensitive patients in the "photosensitivity model", an early phase II study. A total of 12 patients (10 females, 2 males) with a mean age of 21.5 years (range 13-38) were investigated during a 3 day period in 3 centres (France, The Netherlands, Germany), using the same standardised method. The subjects were either treated with a single oral dose of 250 mg, 500 mg, 750 mg or 1000 mg. In addition, 4 patients took 250 mg b.i.d, for 3-5 days, after which they were re-examined. In 9 of 12 photosensitive patients (75%) a clear suppression (3 patients) or abolishment (6 patients) of IPS evoked photoparoxysmal EEG responses was found. This effect appeared to be dose-dependent, the higher the dose the greater the effect; complete abolishment was only seen at dosages of 750 mg and 1000 mg, occurring at peak plasma levels and lasting between 6 and 30 h. There was no indication of pharmacokinetic interaction with concomitant antiepileptic drugs such as valproic acid, ethosuximide or phenobarbitone. No serious side-effects were seen and some patients reported enhancement of their mood. Two patients with myoclonic jerks noticed a clear reduction of their myoclonus, although this was not one of the objectives of the study. In conclusion, levetiracetam showed a clear antiepileptic effect in the photosensitivity model.

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“…Yet as we explained earlier, aspects of this study critically cloud its interpretation. Perhaps the most promising study is the one by Chaudhry et al (1992), which demonstrated an improvement in cognitive functioning of epileptic patients. Regarding this study, it should be noted that reviews have incorrectly reported that the dose was 800 mg/day (cf.…”

Section: Discussionmentioning

confidence: 99%

“…Piracetam has been tested for its effectiveness in ameliorating memory disturbances in epileptic patients. In a study conducted in Pakistan, epileptic patients ranging in age from 10 to 50 years received 2.4 g/day of piracetam either alone or in combination with an antiepileptic drug, and two additional groups received antiepileptic drugs alone (15 patients per group; Chaudhry, Najam, de Mahieu, Raza, & Ahmad, 1992). At baseline, all groups showed a typical decrement in memory performance relative to a control group of 15 people without epilepsy.…”

Section: Piracetammentioning

confidence: 99%

“Brain-Specific” Nutrients: A Memory Cure?

McDaniel

Maier

Einstein

2002

Psychol Sci Public Interest

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We review the experimental evaluations of several widely marketed nonprescription compounds claimed to be memory enhancers and treatments for age-related memory decline. We generally limit our review to double-blind placebo-controlled studies. The compounds examined are phos-phatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antiox-idants (particularly vitamin E). In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. Preliminary findings with humans, though, are limited. For older adults with probable Alzheimer's disease, a single study failed to demonstrate positive effects of PS on memory performance. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests. There is one report of consistent benefits across a number of memory tests for a subset of normal adults who performed more poorly than their peers at baseline. The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory. PC has not proven effective for improving memory in patients with probable Alzheimer's disease. The issue remains open for older adults without serious degenerative neural disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults who scored lower than their peers in baseline testing. Animal studies suggest that piracetam may improve neuronal efficiency, facilitate activity in neurotransmitter systems, and combat the age-related decrease in receptors on the neuronal membrane. However, for patients with probable Alzheimer's disease, as well as for adults with age-associated memory impairment, there is no clear-cut support for a mnemonic benefit of piracetam. Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. In three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo in performance on global cognitive tests reflecting attention, concentration, and memory. Effects on episodic memory per se have been tested minimally, if at all. ALC participates in cellular energy production, a process especially important in neurons, and in removal of toxic accumulation of fatty acids. Animal studies show that ALC reverses the age-related decline in the number of neuron membrane receptors. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups. Significant differences have been reported rarely, however. Whether ALC would have mnemonic benefits for ...

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Clinical use of piracetam in epileptic patients

Cited by 14 publications

References 6 publications

Anticonvulsant Properties of the Novel Nootropic Agent Nefiracetam in Seizure Models of Mice and Rats

Anticonvulsant Properties of the Novel Nootropic Agent Nefiracetam in Seizure Models of Mice and Rats

Photosensitive epilepsy: a model to study the effects of antiepileptic drugs. Evaluation of the piracetam analogue, levetiracetam

“Brain-Specific” Nutrients: A Memory Cure?

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