Benzodiazepine receptor ligands: a patent review (2006 – 2012)

@article{Guerrini2013BenzodiazepineRL,
  title={Benzodiazepine receptor ligands: a patent review (2006 – 2012)},
  author={G. Guerrini and G. Ciciani},
  journal={Expert Opinion on Therapeutic Patents},
  year={2013},
  volume={23},
  pages={843 - 866}
}
Introduction: Ligands at the benzodiazepine site of the GABAA receptor (GABAA-R) act by modulating the effect of GABAA (γ-aminobutyric acid). The selective modulator effects of such ligands are related to the α-subunits type (i.e., α1, α2, α3, and α5), being shown that the α1 subunit is associated with sedative, anticonvulsant and amnesic effects; whereas the α2 and α3 subunits mediate anxiolytic and myorelaxant effects. Recently it was shown the involvement of α5 subunit in pain relief, which… Expand
GABAA receptor subtype modulators in medicinal chemistry: an updated patent review (2014-present)
TLDR
This review covers patents published from 2014 to present on ligands for the benzodiazepine binding site of the GABAARs and finds the presence of the α4- and α5-GABAA receptor subtype ligands as new pharmacological tools for airway hyperresponsiveness, inflammation diseases, and asthma. Expand
Different Benzodiazepines Bind with Distinct Binding Modes to GABAA Receptors
TLDR
It is concluded that different chemically related benzodiazepine ligands interact via distinct binding modes rather than by using a common binding mode. Expand
Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the α5 subunit.
TLDR
As an amide compound with improved stability and kinetic properties, MP-III-022 may represent an optimized tool to study the influence of α5GABAARs on the neuronal pathways related to CNS disorders such as schizophrenia, Alzheimer's disease, Down syndrome or autism. Expand
Endozepines and their receptors: Structure, functions and pathophysiological significance.
TLDR
Current knowledge concerning the various actions of endozepines is reviewed and the physiopathological implications of these regulatory gliopeptides are discussed. Expand
The Neurochemical Mechanisms of the Pharmacological Activities of Inverse Agonists of the Benzodiazepine Binding Site
TLDR
The neurochemical mechanisms of the pharmacological activities of benzodiazepine binding site inverse agonists inhibit chloride currents caused by gamma-aminobutyric acid at low non-physiological concentrations and are able to activate memory formation processes and improve learning. Expand
Insights into Nicotinic Receptor Signaling in Nicotine Addiction: Implications for Prevention and Treatment
TLDR
This review intends to provide insights into recent advances in nAChR signaling, considering the subtypes and subunits of nA ChRs and their roles in nicotinic cholinergic systems, including structure, diversity, functional allosteric modulation, targeted knockout mutations, and rare variations of specific subunits. Expand
Negative modulation of α5 GABAA receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion
TLDR
The results show that certain MK-801-induced memory deficits can be ameliorated by negative modulation of α5 GABAA receptors, and point to the need for further elucidation of their translational relevance to cognitive deterioration in schizophrenia. Expand
Preclinical assessment of the abuse potential of the orexin receptor antagonist, suvorexant
TLDR
Nonclinical findings suggested that suvorexant will have low abuse potential in humans, likely due to its first‐in‐class status, its sedative properties, and the outcome of the clinical abuse potential assessment. Expand
Evaluation of direct-to-patient educational approaches for reducing inappropriate sedative-hypnotic use in community-dwelling older adults
TLDR
This thesis tests the hypothesis that older adults can enable the initiation of benzodiazepine deprescribing when equipped with evidence-based educational material about drug harms and safer non-pharmacological alternatives and addresses some of the observed barriers to sedative-hypnotic depresCribing. Expand
Evaluating the effects of general anesthesia on sleep in children undergoing elective surgery: an observational case–control study
TLDR
In this study, general anesthesia did not result in disturbed sleep or associated negative behavioral changes in otherwise healthy children undergoing elective surgeries of low complexity and Physicians can advise parents that a child's surgery and associated general anesthetic exposure mayNot result in significant changes in postoperative sleep patterns. Expand
...
1
2
...

References

SHOWING 1-10 OF 112 REFERENCES
α-Subunit selective modulators of GABAA receptor function as CNS therapeutics
TLDR
This article focuses on new ligands that are reported to selectively recognise particular α-subunits of GABAA receptors and may thereby offer improved treatments for CNS disorders. Expand
α2-containing GABA(A) receptors: a target for the development of novel treatment strategies for CNS disorders.
GABA(A) receptors have important physiological functions, as revealed by pharmacological studies and experiments involving gene-targeted mouse models, and are the target of widely used drugs such asExpand
Structural Mechanisms Underlying Benzodiazepine Modulation of the GABAA Receptor
TLDR
The role of the γ2Q182-R197 region (Loop F/9) in the modulation of IGABA by positive and negative BZD ligands is explored, demonstrating that γ 2Loop F is a specific transducer of positive BZd modulator binding and is part of the allosteric pathway allowing positive BzD modulator-induced structural changes at the BZ D binding site to propagate through the protein to the channel domain. Expand
GABAA receptor subtype-selective modulators. II. α5-selective inverse agonists for cognition enhancement.
  • J. Atack
  • Chemistry, Medicine
  • Current topics in medicinal chemistry
  • 2011
TLDR
The feasibility of adopting a selective efficacy approach in the identification of α5 selective GABA(A) receptor inverse agonists is demonstrated and the clinical candidate α5IA as well as the structurally-related pharmacological tool compoundα5IA-II are identified. Expand
The quest for the treatment of cognitive impairment: α7 nicotinic and α5 GABAA receptor modulators
TLDR
This article reviews the patents on modulators of α7 nicotinic acetylcholine and GABAA receptors disclosed during the period 2000 – 2006 and seems at present the most important GabAA receptor subtype involved in cognitive processes. Expand
GABAA receptor subtype-selective modulators. I. α2/α3-selective agonists as non-sedating anxiolytics.
  • J. Atack
  • Chemistry, Medicine
  • Current topics in medicinal chemistry
  • 2011
TLDR
T attempts were made to identify subtype-selective compounds that modulate α2/α3 but not α1 receptor function with the prediction that such compounds would be non-sedating anxiolytics, and a structurally-related class of imidazopyridines was explored. Expand
The role of GABA(A) receptor subtypes as analgesic targets.
TLDR
It is suggested that subtype-selective positive modulators of GABA(A) alpha(2/3) receptors might reverse a loss of postsynaptic GABA( a) receptor-mediated inhibitory function in spinal cord, leading to analgesia, and alteration of presynaptic inhibitory neural transmission in chronic pain suggests that drugs that negatively modulate GABA( A) receptorsmight also be effective analgesics. Expand
Nootropic α7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators
TLDR
A selective α7 nAChR-positive allosteric modulator (PAM) from a library of GABAA receptor PAMs is generated, which corrects sensory-gating deficits and improves working memory, effects consistent with cognitive enhancement in rodent models. Expand
The benzodiazepine binding site of GABAA receptors as a target for the development of novel anxiolytics
  • J. Atack
  • Chemistry, Medicine
  • Expert opinion on investigational drugs
  • 2005
TLDR
The advent of molecular genetic and pharmacological approaches has begun to delineate which GABAA receptor subtypes are associated with the various pharmacological effects of the non-selective BZs, raising the possibility of a compound that selectively modulates α2- and/or α3- containing receptors but does not affect α1-containing receptors would be a non-sedating anxiolytic. Expand
Regulation of GABAA Receptor Subunit Expression by Pharmacological Agents
TLDR
Drug development for neuropsychiatric disorders, including epilepsy, alcoholism, schizophrenia, and anxiety, has been ongoing for several years and one key step to extend drug development related to GABAA receptors is likely to require deeper understanding of the adaptational mechanisms of neurons, receptors themselves with interacting proteins, and finally receptor subunits during drug action and in neuropsychiatrics disease processes. Expand
...
1
2
3
4
5
...