- |||||||||| sevoflurane / Generic mfg.
Journal: Prelimbic cortical pyramidal neurons to ventral tegmental area projections promotes arousal from sevoflurane anesthesia. (Pubmed Central) - Mar 19, 2024
In summary, this study affirmed the potential of AMPA receptor inhibition in countering inflammation and tissue apoptosis after myocardial infarction, making it a promising therapeutic target for mitigating myocardial infarction. This study demonstrates that PrLPyr neurons and their projections to the VTA are involved in facilitating emergence from sevoflurane anesthesia, with the PrLPyr -VTA pathway exerting its effects through the activation of NMDA receptors within the VTA.
- |||||||||| Journal: Selective striatal fast-spiking interneuron inhibition induces cortical seizure. (Pubmed Central) - Jan 29, 2024
Thus, striatal FSIs likely play a role in controlling cortical excitability through the cortico-striato-thalamo-cortical pathway. They may contribute to the pathophysiology of focal motor epilepsies by modulating the threshold at which focal motor seizures are triggered.
- |||||||||| Review, Journal: Targeting metaplasticity mechanisms to promote sustained antidepressant actions. (Pubmed Central) - Jan 4, 2024
We conclude that the convergence of these therapeutic mechanisms provides the opportunity for metaplasticity processes to be harnessed as a druggable plasticity mechanism by next-generation therapeutics. Further, targeting metaplastic mechanisms presents therapeutic advantages including decreased dosing frequency and associated diminished adverse responses by eliminating the requirement for the drug to be continuously present.
- |||||||||| vigabatrin / Generic mfg.
Development of a calcium imaging-based drug screening platform for iPSC-derived heterogeneous neuronal cultures (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_6902;
Such synaptic blockers include Vigabatrin, an irreversible inhibitor of GABA transaminase; CNQX, a competitive AMPA receptor antagonist; and DAP-V, a competitive NMDA receptor antagonist (Ben-Menachem, 2011; Honore et al...Continuous blue and green illumination excites the green-shifted and red-shifted GECIs, respectively, within the different sub-types of neurons, which provides a novel platform for single-cell resolution drug screening. Future work will include utilizing the dual-color calcium imaging screening platform in iPSC-derived disease models in which neuronal signaling and connectivity are altered.
- |||||||||| Presynaptic Regulation of Quantal Size at calyx of Held Synapses Following Conductive Hearing Loss (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_4890;
Lastly, bath application of a low-affinity, rapidly dissociating AMPA receptor antagonist ?-DGG revealed that higher concentration of glutamate is packed into the vesicles of hearing loss calyces. In conclusion, our results showed that hearing loss induces presynaptic homeostatic plasticity by increasing vesicular glutamate concentration and decreasing neurotransmitter release probability.
- |||||||||| Journal: Evidence that ultrafast non-quantal transmission underlies synchronized vestibular action potential generation. (Pubmed Central) - Sep 30, 2023
We present several lines of evidence in the guinea pig which reveals the most sensitive vestibular afferents are remarkably fast, much faster than their auditory nerve counterparts. Here, we present neurophysiological and pharmacological evidence that demonstrates this vestibular speed advantage arises from ultrafast NQ electrical synaptic transmission from type I hair cells to their calyx partners.
- |||||||||| Fycompa (perampanel) / Eisai, Catalyst Pharma
Review, Journal: The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy. (Pubmed Central) - Jul 24, 2023
However, recent data show that PER can potentially address many other conditions within epilepsy and beyond. From this perspective, this review aims to examine the new preclinical and clinical studies-especially those produced from 2017 onwards-on AMPA antagonism and PER in conditions such as mesial temporal lobe epilepsy, idiopathic and genetic generalized epilepsy, brain tumor-related epilepsy, status epilepticus, rare epileptic syndromes, stroke, sleep, epilepsy-related migraine, cognitive impairment, autism, dementia, and other neurodegenerative diseases, as well as provide suggestions on future research agenda aimed at probing the possibility of treating these conditions with PER and/or other AMPA receptor antagonists.
- |||||||||| Review, Journal: In the Fast Lane: Receptor Trafficking During Status Epilepticus. (Pubmed Central) - May 15, 2023
Reviewed here is how SE-induced shifts in receptor subunit composition and surface representation increase the excitatory to inhibitory imbalance that sustains seizures and fuels excitotoxicity contributing to chronic sequela such as 'spontaneous recurrent seizures' (SRS). A role for early multimodal therapy is suggested both for treatment of SE and for prevention of long-term co-morbidities.
- |||||||||| sirolimus / Generic mfg.
Journal: Intranasal Administration of Resolvin E1 Produces Antidepressant-Like Effects via BDNF/VEGF-mTORC1 Signaling in the Medial Prefrontal Cortex. (Pubmed Central) - Apr 25, 2023
Intracerebroventricular infusion of resolvin E1 (RvE1), a bioactive metabolite derived from eicosapentaenoic acid, exerts antidepressant-like effects in a mouse model of lipopolysaccharide (LPS)-induced depression; these effects are blocked by systemic injection of rapamycin, a mechanistic target of rapamycin complex 1 (mTORC1) inhibitor...These findings suggest that i.n. administration of RvE1 produces antidepressant-like effects through activity-dependent BDNF/VEGF release in the mPFC and dorsal DG, and mTORC1 activation in the mPFC, but not in the dorsal DG. Thus, RvE1 can be a promising candidate for a novel rapid-acting antidepressant.
- |||||||||| Fycompa (perampanel) / Eisai, Catalyst Pharma
Retrospective data, Journal: Perampanel as Precision Therapy in Rare Genetic Epilepsies. (Pubmed Central) - Apr 14, 2023
Thus, RvE1 can be a promising candidate for a novel rapid-acting antidepressant. Perampanel demonstrated high safety and efficacy in patients with rare genetic epilepsies, especially in SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, CDKL5, NEU1, and POLG, suggesting a targeted effect related to glutamate transmission.
- |||||||||| Journal: Alteration of LHb function prevents the proper exploration of a novel environment. (Pubmed Central) - Mar 6, 2023
In addition, during the first, but not the two consecutive sessions, both treatments prevented a thorough exploration of the OF. Altogether, these results confirm the crucial role played by the LHb in anxiety-related behaviours and further suggest its implication in the exploration of new anxiogenic environments.
- |||||||||| Preclinical, Journal: Intra?LPGi microinjection of glutamate receptors antagonists abolish 17??estradiol?induced analgesic effect in the ovariectomized rats. (Pubmed Central) - Feb 7, 2023
AP5 and CNQX reduced the anti?nociceptive effect of 17??estradiol in the late phase, but not the early phase of licking response in the OVX rats. These results suggested: (i) The intra?LPGi injection of 17??estradiol is satisfactory in producing modest analgesia on the formalin?induced inflammatory pain in the OVX rats; (ii) Co?treatment of glutamate receptors (NMDA and AMPA) antagonists and 17??estradiol in the LPGi nucleus decrease the analgesic effect of 17??estradiol in the OVX rats; (iii) There is a possible association between 17??estradiol and glutamate receptors of the LPGi nucleus on pain coping behavior in the OVX rats.
- |||||||||| methamphetamine / Generic mfg.
Journal: Methamphetamine-induced lethal toxicity in zebrafish larvae. (Pubmed Central) - Nov 22, 2022
These 2 rapid antidepressants have similar, but not identical mechanisms that result in persisting synaptic enhancement, possibly contributing to psychotropic actions. These experiments provide a baseline for the study of the toxicity of related amphetamine compounds in 5-dpf zebrafish as well as a new high-throughput approach for investigating the toxicities of rapidly emerging new psychoactive substances.
- |||||||||| 2R,6R-hydroxynorketamine hydrochloride ((2R,6R)-HNK) / National Institute of Mental Health
Journal: (2R,6R)-hydroxynorketamine (HNK) reverses mechanical hypersensitivity in a model of localized inflammatory pain. (Pubmed Central) - Nov 9, 2022
SIGNIFICANCE: The ketamine metabolite (2R,6R)-HNK reversed mechanical hypersensitivity associated with localized inflammation with onset less than one hour and duration greater than 24 hours in an effect comparable to the NSAID carprofen. Reversal of mechanical hypersensitivity by (2R,6R)-HNK is AMPAR-dependent.
- |||||||||| vigabatrin / Generic mfg.
Dual-color calcium imaging operates as a novel drug screening platform in iPSC-derived heterogeneous neuronal culture systems (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_10713;
Such synaptic blockers include Vigabatrin, an irreversible inhibitor of GABA transaminase; CNQX, a competitive AMPA receptor antagonist; and DAP-V, a competitive NMDA receptor antagonist (Ben-Menachem, 2011; Honore et al., 1998; Davies et al., 1981)...In dual-color calcium imaging, the use of distinct GECIs in a heterogeneous cell culture system provides a novel platform for single-cell resolution drug screening. Future work will include utilizing the dual-color calcium imaging screening platform in iPSC-derived disease models in which neuronal signaling and connectivity are altered.
- |||||||||| Excitatory inputs to somatostatin interneurons modulate context-dependence of the visual cortex (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_8645;
Our results suggest that reducing AMPAR input onto SOM cells enhances recurrent activity, lending support to the idea that regulating recurrent connections among Pyr cells is a key aspect of how SOM cells contribute to shaping visual responses. Moreover, this hints at a complex change in the operating regime of visual cortex circuits based on behavioral state that we will continue to probe in future work.
- |||||||||| Fycompa (perampanel) / Eisai
Retrospective data, Review, Journal, Real-world evidence: The real-world effectiveness and safety of perampanel in Europe: A scoping review. (Pubmed Central) - Aug 31, 2022
There was no relationship between the overall rate of AEs and perampanel dose, perampanel plasma levels, or number of concomitant medications. Our global overview of European observational studies with perampanel provides evidence that this agent is effective and safe in clinical practice in a range of countries, patients, and settings.
- |||||||||| Journal: Glutamate Receptors Mediate Changes to Dendritic Mitochondria in Neurons Grown on Stiff Substrates. (Pubmed Central) - Aug 13, 2022
Treatment of neurons grown on the stiffer gels or glass with the NMDA and AMPA receptor antagonists, 2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively, results in mitochondrial characteristics of neurons grown on the softer substrate. These results suggest that glutamate receptors play important roles in regulating both mitochondrial morphology and dendritic arborization in response to substrate stiffness.
- |||||||||| Journal: Pleiotrophin, nitric oxide and glutamate AMPA receptors in chick cerebellum morphogenesis. (Pubmed Central) - May 20, 2022
Interestingly, blockage of AMPA receptors had no effect; while NOS inhibition resulted in transient age- and region-specific increases of EGL granule progenitor cell proliferation at earlier stages, but decreased the post-mitotic granule cells at folia apices, at a later stage HH41 (E15 day). Taken all together, NO had a transient anti-proliferative effect in EGL similar to mammalian cerebellum, acting as a modulator of the EGL function at different stages, suggesting its possible implication in complex processes guiding cerebellar cytoarchitecture and folia formation.
- |||||||||| ifenprodil tartrate / Chiba University Hospital
Preclinical, Journal: NMDA Receptor Neuropharmacology: NMDA Receptor-mediated Calcium Transients are Attenuated by Agmatine in Mouse Spinal Cord Dorsal Horn. (Pubmed Central) - May 14, 2022
Other NMDAr antagonists including AP5 and ifenprodil, showed dose-dependent inhibition of NMDAr-mediated calcium transients, supporting that the newly developed calcium imaging assay is NMDAr specific. These data suggest that agmatine attenuates NMDAr-mediated calcium transients in the spinal cord dorsal horn, which is consistent with our previous research demonstrating that agmatine is an effective inhibitor of NMDAr in the spinal cord.
- |||||||||| dizocilpine (MK801) / Merck (MSD)
Centrally administered corticotropin-releasing factor induces facilitation of the rat micturition via brain glutamatergic receptors (Room 228) - Apr 10, 2022 - Abstract #AUA2022AUA_1467;
In some rats, effects of icv pretreated CP154526 (CP, CRF1 antagonist, 30 or 100 nmol/rat), K41498 (K, CRF2 antagonist, 30 nmol/rat), MK-801 (MK, NMDA receptor antagonist, 3 or 10 nmol/rat) or DNQX (AMPA receptor antagonist, 1 or 3 nmol/rat) on the CRF (3 nmol/rat, icv)-induced responses were examined...Compared to the vehicle-treated group, CRF significantly reduced single-voided volume and bladder capacity without changing post void residual volume or voiding efficiency (Table 1). Conclusions : Centrally administered CRF induces facilitation of the rat micturition via brain CRF1, NMDA and AMPA receptors, therefore, brain CRF1 receptors might be new therapeutic targets for neurogenic bladder overactivity.
- |||||||||| Huntexil (pridopidine) / Prilenia, Xadago (safinamide) / Meiji Seika, Eisai, Valeo Pharma, Zambon, Supernus Pharma, mesdopetam (IRL790) / Ipsen
Review, Journal: Non-dopaminergic approaches to the treatment of motor complications in Parkinson's disease. (Pubmed Central) - Apr 8, 2022
We also review compounds with complex pharmacological properties that are already used clinically or about to enter an advanced phase of clinical development (amantadine, safinamide, zonisamide, pridopidine, mesdopetam). We conclude with an outlook on possible directions to address unmet needs and improve the chance of successful translation in this therapeutic area.
- |||||||||| Preclinical, Journal: Increase in brain L-lactate enhances fear memory in diabetic mice: involvement of glutamate neurons. (Pubmed Central) - Mar 23, 2022
In addition, injection of NBQX into the amygdala and hippocampus significantly inhibited duration of freezing in STZ-induced diabetic mice. These results suggest that L-lactate levels are increased in the amygdala and hippocampus in diabetic mice, which may enhance fear memory though activation of glutamatergic function in the amygdala and hippocampus.
- |||||||||| Preclinical, Journal: Testing of the therapeutic efficacy and safety of AMPA receptor RNA aptamers in an ALS mouse model. (Pubmed Central) - Mar 23, 2022
A 12-wk continuous, intracerebroventricular infusion of aptamers to AR2 mice reduced the progression of motor dysfunction, normalized TDP-43 mislocalization, and prevented death of motor neurons. Our results demonstrate that the use of AMPA receptor aptamers as a novel class of AMPA receptor antagonists is a promising strategy for developing an ALS treatment approach.
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