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Nootropic α7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators
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.
cAMP Signaling Compartmentation: Adenylyl Cyclases as Anchors of Dynamic Signaling Complexes
An argument is made for adenylyl cyclases being central to the formation and maintenance of these signaling complexes, making the characterization of cAMP signaling compartments daunting.
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
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
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.
PDE8 Is Expressed in Human Airway Smooth Muscle and Selectively Regulates cAMP Signaling by &bgr;2‐Adrenergic Receptors and Adenylyl Cyclase 6
PDE8 is expressed in lipid rafts of HASM cells, where it specifically regulates &bgr;2‐adrenergic receptor AC6 signaling without effects on signaling by the E prostanoid receptors 2/4‐AC2 complex, and may represent a novel therapeutic target to modulate HASM responsiveness and airway remodeling.
Pharmacological profile of a 17β-heteroaryl-substituted neuroactive steroid
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
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
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.