Neuropharmacology

Journal: Neuropharmacology

Publisher

Elsevier

ISSN

0028-3908
1873-7064

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Publications 1 - 10 of 29

Reactive and predictive homeostasis: Roles of orexin/hypocretin neurons
Burdakov, Denis (2019)
Neuropharmacology
The clobazam metabolite N-desmethyl clobazam is an α2 preferring benzodiazepine with an improved therapeutic window for antihyperalgesia
Ralvenius, William T.; Acuña, Mario A.; Benke, Dietmar; et al. (2016)
Neuropharmacology
Data from genetically modified mice suggest that benzodiazepine (BDZ)-site agonists with improved selectivity for α2-subtype GABAA receptors (α2GABAAR) are potentially useful for the treatment of neuropathic pain. Subtype-selective compounds available for preclinical tests in rodents support this concept but have not been approved for human use, hindering proof-of-concept studies in patients. We recently proposed that N-desmethyl clobazam (NDMC), the main metabolite of the licensed BDZ clobazam (CBZ), is responsible for most of the antihyperalgesia observed in mice after CBZ administration. In order to assess a potentially favorable pharmacological profile of NDMC, we analyzed differences in the GABAAR subtype specificity of CBZ, NDMC and diazepam (DZP) in recombinant receptors. DZP and CBZ potentiated sedating α1GABAARs and antihyperalgesic α2GABAARs with similar efficacies, whereas NDMC preferred α2GABAARs over α1GABAARs across a wide concentration range. In vivo, DZP and NDMC reduced neuropathic pain at doses between 3 and 30 mg/kg. At these doses, DZP had strong locomotor sedating effects while NDMC caused no or only weak sedation. Sedative effects of NDMC became apparent when the action of NDMC was restricted to α1GABAARs. However, when GABAAR point-mutated mice were studied that allow the analysis of antihyperalgesia and sedation in isolation, we found that, compared to DZP, NDMC had a significantly improved therapeutic window, consistent with its more favorable α2/α1 in vitro activity ratio. Given that NDMC should share the safety profile of its parent compound CBZ, it should be well-suited for proof-of-concept studies in human volunteers or patients.
NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin
Alagarsamy, Sudar; Saugstad, Julie; Warren, Lee; et al. (2005)
Neuropharmacology
How may the hypothalamus control distinct types and stages of memory?
Burdakov, Denis; Peleg-Raibstein, Daria (2025)
Neuropharmacology
Memory is a complex and multifaceted cognitive function integral to all aspects of survival across species. It involves short-term and long-term components, which are supported by distinct yet interconnected brain systems, each specialized in processing distinct types of information. These systems interact in an integrated and dynamic manner, allowing for the encoding, consolidation, retrieval, and updating of memories. In this review, we explore the role of orexin and melanin-concentrating hormone (MCH) neurons, clustered primarily within lateral hypothalamus (LH), in orchestrating these memory processes. We consider its demonstrated and potential contributions across memory phases (e.g., short-term, long-term), transitional processes (e.g., consolidation, retrieval), and memory types (e.g., declarative, nondeclarative). Particular attention is given to its neuropeptides, orexin and. MCH, which have been implicated in modulating arousal, sleep, and neural plasticity - key factors in memory formation and maintenance. While orexin and MCH neurons have direct (arousal-independent) synaptic effects relevant to memory, their overall influence on memory processes is likely to include their established roles in regulating arousal, vigilance, and sleep. We further link these roles to the LH's traditional view as a nutritional sensor and regulator of arousal states, highlighting its unique position at the intersection of homeostatic and cognitive functions. By providing a unified perspective on the LH's involvement in memory, this work aims to bridge gaps in our understanding of its broader cognitive significance.
A regulatory pathway linking caffeine action, mood and the diurnal clock
Trautmann, Charlotte; Burek, Dominika; Hübner, Christian A.; et al. (2020)
Neuropharmacology
HZ166, a novel GABA(A) receptor subtype-selective benzodiazepine site ligand, is antihyperalgesic in mouse models of inflammatory and neuropathic pain
Di Lio, Alessandra; Benke, Dietmar; Besson, Marie; et al. (2011)
Neuropharmacology
Cognitive, behavioral and metabolic effects of oral galactose treatment in the transgenic Tg2576 mice
Babic Perhoc, Ana; Osmanovic Barilar, Jelena; Knezovic, Ana; et al. (2019)
Neuropharmacology
GABAA receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts
Benke, Dietmar; Barberis, Andrea; Kopp, Sascha; et al. (2009)
Neuropharmacology
A differential activation of dopamine output in the shell and core of the nucleus accumbens is associated with the motor responses to addictive drugs
Lecca, Daniele; Piras, Giovanna; Driscoll, Peter; et al. (2004)
Neuropharmacology
Global slowing of network oscillations in mouse neocortex by diazepam
Scheffzük, Claudia; Kukushka, Valeriy I.; Vyssotski, Alexei L.; et al. (2013)
Neuropharmacology

Publications 1 - 10 of 29

Journal: Neuropharmacology

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