Neuroscience Research Compound · For laboratory research use only
Aniracetam (1-(4-methoxybenzoyl)-2-pyrrolidinone, also 1-p-anisoyl-2-pyrrolidinone) is a pyrrolidinone-type compound of the racetam family1,5. Its best-characterised action is positive allosteric modulation of AMPA-type glutamate receptors, described in Xenopus oocytes and rat hippocampal slices in 19901 and later examined at the structural level2.
Rodent studies have examined its metabolites, cholinergic transmission and behaviour in models of anxiety and cognition3,4,5,6. Several of its effects in vivo have been attributed to its major metabolites, N-anisoyl-GABA and p-anisic acid3,4.
As described in the research literature
As described in the research literature, aniracetam potentiated quisqualate and AMPA receptor responses in Xenopus oocytes expressing rat brain mRNA, increasing the conductance change without altering agonist affinity or ion selectivity, and left kainate, NMDA and GABA responses unaffected. It also potentiated excitatory postsynaptic potentials in rat hippocampal slices1.
Co-crystal structures of the GluR2 S1S2 ligand-binding domain showed aniracetam bound within the dimer interface at a site adjacent to the hinge of the ligand-binding clamshell. The authors proposed that it slows receptor deactivation by stabilising the closed-cleft, glutamate-bound conformation, and point mutations at the site disrupted potentiation2.
In stroke-prone spontaneously hypertensive rats, local perfusion of the metabolites N-anisoyl-GABA and p-anisic acid increased acetylcholine release in thalamic, hippocampal and prefrontal regions, whereas no effect of aniracetam itself was found in that preparation3.
What published studies have examined
Xenopus oocyte and rat hippocampal slice recordings characterised potentiation of AMPA-type responses1. Crystallography of the GluR2 ligand-binding domain, with rapid solution exchange patch-clamp recordings of binding-site mutants, located the modulator site2.
Choline acetyltransferase activity and acetylcholine release were measured by in vivo microdialysis in stroke-prone spontaneously hypertensive rats, comparing aniracetam with its metabolites3.
Sources [3]
Social interaction, elevated plus-maze and conditioned fear stress tests in mice were used, with receptor antagonists to probe nicotinic, 5-HT2A and dopamine D2 receptor involvement and with individual metabolites compared against the parent compound4.
Sources [4]
A study in naive adult C57BL/6J mice examined spatial, associative and motor learning, odour discrimination, locomotion, anxiety-related and repetitive behaviour, and found no differences between treated, placebo and naive groups6. A review summarises the wider range of rodent models in which aniracetam has been examined5.
Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.
Ito I, Tanabe S, Kohda A, et al. The Journal of Physiology, 1990.
Mechanism of positive allosteric modulators acting on AMPA receptors.
Jin R, Clark S, Weeks AM, et al. The Journal of Neuroscience, 2005.
Activation of the reticulothalamic cholinergic pathway by the major metabolites of aniracetam.
Nakamura K, Shirane M European Journal of Pharmacology, 1999.
Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism.
Nakamura K, Kurasawa M European Journal of Pharmacology, 2001.
Aniracetam: its novel therapeutic potential in cerebral dysfunctional disorders based on recent pharmacological discoveries.
Nakamura K CNS Drug Reviews, 2002.
Aniracetam does not alter cognitive and affective behavior in adult C57BL/6J mice.
Elston TW, Pandian A, Smith GD, et al. PLoS One, 2014.
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