Aniracetam

Aniracetam is a nootropic drug in senile dementia [1].

Aniracetam (Ro 13-5057) has a piracetam-like chemical structure, 1-p-anisoyl-2-pyrrolidinone. It is selected from a series of related compounds because of its effect in impaired cognitive functions in rodents. In rats, the administration of aniracetam (30mg/kg orally) markedly prevents the CO2 induced impairment of acquisition. It also significantly increases the percentage of rats showing retention of the learned task in both the scopolamine induced transient retrograde amnesia model (50mg/kg orally) and the electroconvulsive shock induced memory disruption model (50mg/kg orally). Besides that, aniracetam can prevent the disruptive effect caused by chloramphenicol or cycloheximide (30mg/kg orally) [1, 2].

References:
[1] MIZUKI Y, YAMADA M, KATO I, et al. Effects of aniracetam, a nootropic drug, in senile dementia. A preliminary report.: A Preliminary Report. The Kurume medical journal, 1984, 31(2): 135-143.
[2] Cumin R, Bandle E F, Gamzu E, et al. Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents. Psychopharmacology, 1982, 78(2): 104-111.

Clinical efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors, in patients with cognitive impairment: a comparative open study.[Pubmed:22070796]

CNS Neurosci Ther. 2012 Apr;18(4):302-12.

INTRODUCTION: Dementia constitutes an increasingly prevalent cognitive disorder with serious socioeconomic implications. AIMS: In the present study, we aimed to evaluate the efficacy of Aniracetam, either as monotherapy or combined with cholinesterase inhibitors (ChEIs), in terms of several neuropsychological parameters, in a considerable number of patients with dementia. RESULTS: In our prospective, open-label study, we enrolled a total of 276 patients (mean age 71 +/- 8 years, 95 males) with cognitive disorders. Our study population comprised four groups: no treatment group (n = 75), Aniracetam monotherapy group (n = 58), ChEIs monotherapy group (n = 68), and group of combined treatment (n = 68). Patients were examined with validated neuropsychological tests at baseline, 3, 6, and 12 months of treatment. In patients treated with Aniracetam, all studied parameters were adequately maintained at 6 and 12 months, while emotional state was significantly improved at 3 months. In patients treated with ChEIs, we observed a significant cognitive deterioration at 12 months. The comparison between Aniracetam and ChEIs in patients with relatively mild dementia (15 Aniracetam at 6 months and improved functionality at 3 months. Comparing Aniracetam monotherapy with combined treatment in the same population, Aniracetam performed better in the cognitive scale at 6 months, and displayed a notable tendency for enhanced mood at 12 months and improved functionality at 6 months. CONCLUSIONS: Our findings indicate that Aniracetam (a nootropic compound with glutamatergic activity and neuroprotective potential) is a promising option for patients with cognitive deficit of mild severity. It preserved all neuropsychological parameters for at least 12 months, and seemed to exert a favorable effect on emotional stability of demented patients.

Aniracetam does not alter cognitive and affective behavior in adult C57BL/6J mice.[Pubmed:25099639]

PLoS One. 2014 Aug 6;9(8):e104443.

There is a growing community of individuals who self-administer the nootropic Aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, Aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of Aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of Aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naive C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that Aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs.

Subnanogram determination of aniracetam in pharmaceutical preparations and biofluids by flow injection analysis with chemiluminescence detection based on its enhancement of the myoglobin-luminol reaction.[Pubmed:22165010]

J AOAC Int. 2011 Sep-Oct;94(5):1461-6.

A novel flow injection chemiluminescence method with a myoglobin-luminol system is described for determining Aniracetam. Myoglobin-bound Aniracetam produced a complex that catalyzed the chemiluminescence reaction between luminol and myoglobin, leading to fast chemiluminescence. The chemiluminescence intensity in the presence of Aniracetam was remarkably enhanced compared with that in the absence of Aniracetam. Under the optimum reaction conditions the chemiluminescence increment produced was proportional to the concentration of Aniracetam in the range of 0.1-1000.0 ng/mL (R2 = 0.9992), with a detection limit of 0.03 ng/mL (3delta). At a flow rate of 2.0 mL/min, the whole process, including sampling and washing, could be completed in 0.5 min, offering a sampling efficiency of 120/h; the RSD was less than 3.0% (n = 5). The method was satisfactory for determination of Aniracetam in pharmaceutical preparations and human urine and serum samples. A possible mechanism of the reaction is also discussed.

Development and validation of a liquid chromatographic method for the simultaneous determination of aniracetam and its related substances in the bulk drug and a tablet formulation.[Pubmed:21742456]

J Pharm Biomed Anal. 2011 Nov 1;56(3):615-22.

Simultaneous determination of Aniracetam and its related impurities (2-pyrrolidinone, p-anisic acid, 4-p-anisamidobutyric acid and (p-anisoyl)-4-methyl-2-pyrrolidinone) was accomplished in the bulk drug and in a tablet formulation using a high performance liquid chromatographic method with UV detection. Separation was achieved on a Hypersil BDS-CN column (150 mm x 4.0 mm, 5 mum) using a gradient elution program with solvent A composed of phosphate buffer (pH 4.0; 0.010 M) and solvent B of acetonitrile-phosphate buffer (pH 4.0; 0.010 M) (90:10, v/v). The flow rate of the mobile phase was 1.0 mL min(-1) and the total elution time, including the column re-equilibration, was approximately 20 min. The UV detection wavelength was varied appropriately among 210, 250 and 280 nm. Injection volume was 20 muL and experiments were conducted at ambient temperature. The developed method was validated in terms of system suitability, selectivity, linearity, range, precision, accuracy, limits of detection and quantification for the impurities, short term and long term stability of the analytes in the prepared solutions and robustness, following the ICH guidelines. Therefore, the proposed method was suitable for the simultaneous determination of Aniracetam and its studied related impurities.

Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus.[Pubmed:1660156]

Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10936-40.

Aniracetam is a nootropic drug that has been shown to selectively enhance quisqualate receptor-mediated responses in Xenopus oocytes injected with brain mRNA and in hippocampal pyramidal cells [Ito, I., Tanabe, S., Kohda, A. & Sugiyama, H. (1990) J. Physiol. (London) 424, 533-544]. We have used patch clamp recording techniques in hippocampal slices to elucidate the mechanism for this selective action. We find that Aniracetam enhances glutamate-evoked currents in whole-cell recordings and, in outside-out patches, strongly reduces glutamate receptor desensitization. In addition, Aniracetam selectively prolongs the time course and increases the peak amplitude of fast synaptic currents. These findings indicate that Aniracetam slows the kinetics of fast synaptic transmission and are consistent with the proposal [Trussell, L. O. & Fischbach, G. D. (1989) Neuron 3, 209-218; Tang, C.-M., Dichter, M. & Morad, M. (1989) Science 243, 1474-1477] that receptor desensitization governs the strength of fast excitatory synaptic transmission in the brain.

Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.[Pubmed:1975272]

J Physiol. 1990 May;424:533-43.

1. Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a nootropic drug Aniracetam (1-p-anisoyl-2-pyrrolidinone) was investigated using Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices. 2. Aniracetam potentiates the iQA responses induced in Xenopus oocytes by rat brain mRNA in a reversible manner. This effect was observed above the concentrations of 0.1 mM. Kainate. N-methyl-D-aspartate and gamma-aminobutyric acid responses induced in the same oocytes were not affected. 3. The specific potentiation of iQA responses was accompanied by an increase in the conductance change of iQA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) responses, but the affinity of receptors for agonist and the ion-selectivity of the channels (reversal potentials) were not changed. 4. Aniracetam reversibly potentiated the iQA responses recorded intracellularly from the pyramidal cells in the CA1 region of rat hippocampal slices. The excitatory postsynaptic potentials (EPSPs) in Schaffer collateral-commissural-CA1 synapses were also potentiated by Aniracetam. 5. Population EPSPs recorded in the mossy fibre-CA3 synapses as well as Schaffer-commissural synapses were also potentiated by Aniracetam. The amplitudes of the potentiation were not changed by the formation of long-term potentiation.