Neuroscience Research Compound · For laboratory research use only
Also known as NS-105, LAM-105
Fasoracetam ((5R)-5-(piperidine-1-carbonyl)pyrrolidin-2-one, also NS-105, LAM-105 and NFC-1) is a pyroglutamide-type racetam developed by Nippon Shinyaku. In the research literature it is usually studied as the monohydrate, (+)-5-oxo-D-prolinepiperidinamide monohydrate1,4. Its solid-state forms, two hydrates and one anhydrous form, were characterised by single-crystal X-ray analysis in 20177.
Most of the published work comes from rat brain tissue, cultured neurons and rodent behavioural models, with a focus on metabotropic glutamate receptors, adenylate cyclase signalling and GABA-B receptors1,2,3,4,5. Its absorption, metabolism and excretion have been characterised in rats, dogs and monkeys6.
As described in the research literature
As described in the research literature, NS-105 modulated cAMP formation in rat cerebral cortex in two directions: it inhibited forskolin-stimulated cAMP formation in membranes, but enhanced it in pertussis toxin-pretreated membranes. Both actions were mimicked by a metabotropic glutamate receptor (mGluR) agonist and blocked by an mGluR antagonist, and NS-105 did not displace binding at a range of neurotransmitter receptors1. Similar bidirectional effects were reported in cultured mouse cortical neurons2.
Later work using selective antagonists and antisense oligonucleotides attributed the inhibitory action to group II and group III mGluR subclasses and the facilitatory action to group I3. In repeated-exposure rat studies, NS-105 was associated with an increased number of GABA-B receptors in the cerebral cortex without changes in beta-adrenoceptor or 5-HT2 receptor binding, and NS-105 did not inhibit monoamine uptake in vitro4.
What published studies have examined
Rat cortical slices and membranes1, cultured mouse cortical neurons2 and subclass-selective tools3 were used to characterise how NS-105 modulates adenylate cyclase activity through mGluRs coupled to Gi/Go and Gs proteins, and its interaction with the GABA-B agonist baclofen.
Forced swimming and learned helplessness tests in rats were combined with receptor binding measurements after repeated exposure4. Memory disruption models in rats, induced by scopolamine, nucleus basalis lesions, AF64A, baclofen, cerebral ischaemia and electroconvulsive shock, were used alongside measures of acetylcholine release, high-affinity choline uptake and choline acetyltransferase activity5.
Radiolabelled NS-105 was used to study absorption, metabolism, excretion and protein binding in rats, dogs and monkeys6. Thermal and structural analysis identified the hydrate form I as the most stable form under ambient conditions7.
A 5-week open-label study with a single-blind placebo week was designed to examine safety, pharmacokinetics and responsiveness in 30 adolescents aged 12 to 17 with ADHD carrying variants in metabotropic glutamate receptor network genes (NCT02286817)8.
Sources [8]
Involvement of metabotropic glutamate receptors in Gi- and Gs-dependent modulation of adenylate cyclase activity induced by a novel cognition enhancer NS-105 in rat brain.
Oka M, Itoh Y, Shimidzu T, et al. Brain Research, 1997.
A novel cognition enhancer NS-105 modulates adenylate cyclase activity through metabotropic glutamate receptors in primary neuronal culture.
Oka M, Itoh Y, Tatsumi S, et al. Naunyn-Schmiedeberg's Archives of Pharmacology, 1997.
Role of metabotropic glutamate receptor subclasses in modulation of adenylyl cyclase activity by a nootropic NS-105.
Hirouchi M, Oka M, Itoh Y, et al. European Journal of Pharmacology, 2000.
Effect of a novel cognition enhancer NS-105 on learned helplessness in rats: possible involvement of GABA(B) receptor up-regulation after repeated treatment.
Shimidzu T, Itoh Y, Oka M, et al. European Journal of Pharmacology, 1997.
Involvement of cholinergic and GABAergic systems in the reversal of memory disruption by NS-105, a cognition enhancer.
Ogasawara T, Itoh Y, Tamura M, et al. Pharmacology, Biochemistry, and Behavior, 1999.
Pharmacokinetics of NS-105, a novel cognition enhancer. 1st communication: absorption, metabolism and excretion in rats, dogs and monkeys after single administration of 14C-NS-105.
Mukai H, Sugimoto T, Ago M, et al. Arzneimittel-Forschung, 1999.
A Study of Fasoracetam's Solid State Forms: A Potential Anti-Alzheimer Pharmaceutical.
Harmsen B, Robeyns K, Wouters J, et al. Journal of Pharmaceutical Sciences, 2017.
Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling.
Elia J, Ungal G, Kao C, et al. Nature Communications, 2018.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.