WAY-100635 is a potent dopamine D4 receptor agonist

@article{Chemel2006WAY100635IA,
  title={WAY-100635 is a potent dopamine D4 receptor agonist},
  author={Benjamin Reed Chemel and Bryan L. Roth and Blaine N. Armbruster and Val J. Watts and David E. Nichols},
  journal={Psychopharmacology},
  year={2006},
  volume={188},
  pages={244-251}
}
Rationale and objectivesWAY-100635 is a prototypical 5-HT1A receptor antagonist and has been used widely as a pharmacological probe to investigate the distribution and function of 5-HT1A receptors. Results from our studies suggested that WAY-100635 was potently inducing effects unrelated to its 5-HT1A receptor affinity. In the present work, we evaluated the in vitro pharmacology of this compound at two D2-like receptor subtypes.MethodThe functional properties and binding affinities of WAY… 

Structural Insights into 5-HT1A/D4 Selectivity of WAY-100635 Analogues: Molecular Modeling, Synthesis, and in Vitro Binding

TLDR
In silico investigations revealed two key interactions for the 5-HT1A/D4 selectivity of WAY-100635 and analogues and a hydrogen bond only found with the Ser 7.36 of D4 receptor appeared to be the key for a higher D4 affinity for newly synthesized aza analogues.

WAY 100635 produces discriminative stimulus effects in rats mediated by dopamine D4 receptor activation

TLDR
The results indicate that the discriminative stimulus effect produced by WAY 100635 is mediated by activation of dopamine D4 receptors.

A HYDROGEN BOND INFLUENCES THE 5-HT1A/D4 SELECTIVITY OF WAY-100635 ANALOGUES: AN IN SILICO APPROACH

TLDR
Various chemical modifications of the WAY-100635 structure were carried out in order to improve its 5-HT 1A versus D 4 selectivity and decrease the selectivity of the acyl group.

5-HT1A receptor pharmacophores to screen for off-target activity of α1-adrenoceptor antagonists

TLDR
The insights and knowledge gained through the development of the new 5-HT1A-R pharmacophores will greatly aid in the design and synthesis of derivatives of the lead compound, and allow the generation of more efficacious and selective ligands.

Ligand-Specific Roles for Transmembrane 5 Serine Residues in the Binding and Efficacy of Dopamine D1 Receptor Catechol Agonists

TLDR
The hypothesis that the decreased D1 activity of chroman analogs results from a ligand intramolecular hydrogen bond that impairs the ability of the catechol to engage the receptor is supported.

Agonist and antagonist properties of antipsychotics at human dopamine D4.4 receptors: G-protein activation and K+ channel modulation in transfected cells.

TLDR
The in-vitro profile of over 30 ligands at recombinant hD4.4 receptors indicates that, unlike conventional or 'atypical' antipsychotics, several 'third generation' agents display D4 receptor partial agonism that may be sufficient to influence physiological D4 receptors activity in vivo.

Differential Effects of M1 and 5-Hydroxytryptamine1A Receptors on Atypical Antipsychotic Drug-Induced Dopamine Efflux in the Medial Prefrontal Cortex

TLDR
DA efflux in the mPFC induced by the atypical antipsychotic drugs clozapine, risperidone, and olanzapine is also mediated by M1 receptor stimulation and results suggest that the AC260584, NDMC-, and clozAPine-induced DA eff Lux in themPFC is mediated directly by mP FC M1 receptors.

Cannabidiol Acts at 5-HT1A Receptors in the Human Brain: Relevance for Treating Temporal Lobe Epilepsy

TLDR
Evaluated cell membranes show that CBD interacts with human 5-HT1A receptors of the hippocampus and temporal neocortex, and at low concentrations, the effect of CBD upon Gi/o protein activation is limited, however, at high concentrations, CBD acts as an inverse agonist of 5- HT1A receptor.
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