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Negative Allosteric Modulation of Nicotinic Acetylcholine Receptors Blocks Nicotine Self-Administration in Rats
TLDR
UCI-30002 represents validation of the concept that negative allosteric modulators may have significant benefits as a strategy for treating nicotine addiction and encourages the development of subtype-selective modulators.
First in human trial of a type I positive allosteric modulator of alpha7-nicotinic acetylcholine receptors: Pharmacokinetics, safety, and evidence for neurocognitive effect of AVL-3288
TLDR
The trial demonstrates that a type I PAM can be safely administered to humans and that it has potential positive neurocognitive effects in central nervous system (CNS) disorders.
Allosteric Modulation of Related Ligand-Gated Ion Channels Synergistically Induces Long-Term Potentiation in the Hippocampus and Enhances Cognition
TLDR
Combined transient application of two allosteric modulators that individually inhibit α5 GABAARs and enhance α7 nAChRs causes long-term potentiation of mossy fiber stimulation-induced excitatory postsynaptic currents (EPSC) from CA1 pyramidal neurons of rat hippocampal slices.
Allosteric modulation of nicotinic and GABAA receptor subtypes differentially modify autism-like behaviors in the BTBR mouse model
TLDR
It is suggested that compounds that have selective activities at GABAAR subtypes and the &agr;7 nAChR PAMs may address the core symptoms and comorbidities of autism.
Pharmacological profile of a 17β-heteroaryl-substituted neuroactive steroid
TLDR
UCI-50027 is an orally active neuroactive steroid with pharmacological activity consistent with a gamma-aminobutyric acid(A) receptor PAM that has an improved separation between anticonvulsant/anxiolytic and rotarod effects, potent activity as an anticonVulsant and anxIOlytic when compared to ganaxolone.
Modifying quinolone antibiotics yields new anxiolytics
Patients taking fluoroquinolone antibiotics such as norfloxacin exhibit a low incidence of convulsions and anxiety. These side effects probably result from antagonism of the neurotransmitter
Limiting Activity at β1-Subunit-Containing GABAA Receptor Subtypes Reduces Ataxia
TLDR
These findings provide an alternative strategy for designing anxioselective allosteric modulators of the GABAAR with BZ-like anxiolytic efficacy by reducing or eliminating activity at β1-subunit-containing GABAARs.
Reversible lipidization for the oral delivery of leu-enkephalin
TLDR
The results indicate that like its disulfide-based counterpart, amine-based REAL may be an enabling technology which can be applied to enhance metabolic stability, increase oral absorption, and preserve and possibly prolong the pharmacological activity of peptide drugs.
Design, synthesis, and activity of a series of arylpyrid-3-ylmethanones as type I positive allosteric modulators of α7 nicotinic acetylcholine receptors.
TLDR
These compounds are potent type I positive allosteric modulators of α7 nAChRs that may have therapeutic value in restoring impaired sensory gating and cognitive deficits in schizophrenia and Alzheimer's disease.
Limited central side effects of a β-subunit subtype-selective GABAA receptor allosteric modulator
TLDR
Results suggest that β2/3-subunit subtype-selective GABAA receptor-positive allosteric modulators not only have reduced sedative liability, but also a reduction in other central side effects commonly associated with broader GabAA receptor activation.
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