WAY-100635 is a potent dopamine D4 receptor agonist

@article{Chemel2006WAY100635IA,
  title={WAY-100635 is a potent dopamine D4 receptor agonist},
  author={Benjamin R. 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… Expand
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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. Expand
A HYDROGEN BOND INFLUENCES THE 5-HT1A/D4 SELECTIVITY OF WAY-100635 ANALOGUES: AN IN SILICO APPROACH
WAY-100635 is widely used in vitro and in vivo as an antagonist of 5-HT 1A receptors [1]. In terms of pharmacological tools and pharmacological investigations, the ideal reference molecule would beExpand
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References

SHOWING 1-10 OF 23 REFERENCES
A pharmacological profile of the selective silent 5-HT1A receptor antagonist, WAY-100635.
TLDR
In behavioural models, WAY-100635 itself induced no overt behavioural changes but potently antagonised the behavioural syndrome induced by 8-OH-DPAT in the rat and guinea-pig, and data indicate that WAY- 100635 will be used as a standard antagonist in further studies of 5-HT1A receptor function. Expand
Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonist
TLDR
In vitro electrophysiological studies demonstrated that WAY-100635 had no 5-HT1A receptor agonist actions, but dose-dependently blocked the effects of agonists at both the postsynaptic5-HT 1A receptor in the CA1 region of the hippocampus, and the somatodendritic 5-ht1A receptors located on dorsal raphe 5- HT neurones. Expand
Silent 5-HT1A receptor antagonists: utility as research tools and therapeutic agents.
TLDR
The pharmacological properties of the first selective silent 5-HT1A receptor antagonists that have been recently discovered are reviewed and the potential therapeutic utility of these novel compounds are discussed. Expand
Aripiprazole, A Novel Atypical Antipsychotic Drug with a Unique and Robust Pharmacology
TLDR
The results support the hypothesis that the unique actions of aripiprazole in humans are likely a combination of ‘functionally selective’ activation of D2 (and possibly D3)-dopamine receptors, coupled with important interactions with selected other biogenic amine receptors—particularly 5-HT receptor subtypes (5-HT1A, 5- HT2A). Expand
The pharmacological characterization of a novel selective 5-hydroxytryptamine1A receptor antagonist, NAD-299.
TLDR
NAD-299 competitively antagonized the 8-hydroxy-2-(di-n-propylamino)tetralin-induced 5-HT behavioral effects, hypothermia, corticosterone secretion and inhibition of passive avoidance behavior without causing any actions of their own. Expand
Short- and long-term heterologous sensitization of adenylate cyclase by D4 dopamine receptors
TLDR
Long-term agonist-induced sensitization of adenylate cyclase by the D4 receptor may involve mechanisms that do not contribute to short-term sensitization, implying a role for Gi/Go proteins in heterologous sensitization. Expand
Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11 C]WAY-100635.
TLDR
The acquired data provide exquisite delineation of 5-HT1A receptors in brain, with the ratio of radioactivity uptake in receptor-rich regions, such as medial temporal cortex, to that in receptors-devoid cerebellum reaching 25 by 60 min after radioligand injection. Expand
In vivo intrinsic efficacy of the 5-HT1A receptor antagonists NAD-299, WAY-100,635 and (S)-(-)-UH-301 at rat brain monoamine receptors 1 Presented in part at the `9th ECNP Congress', Amsterdam, September 21–25, 1996 (Ahlenius et al., 1996). 1
TLDR
It is concluded that S(-)-UH-301, but not WAY-100,635 or NAD-299, displays intrinsic efficacy at brain 5-HT1A and DA D2/3 receptors, whereas WAY- 100,635 behaves as a DA D 2/3 receptor antagonist. Expand
Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system
TLDR
Future research should be directed towards: improvement of the metabolic stability in primates; development of a fluorinated radioligand which can be produced in large quantities and production of a radioiodinated or technetium-labelled ligand for SPET. Expand
2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a selective dopamine D4 receptor antagonist
TLDR
A-381393 is a novel selective D4 antagonist that will enhance the ability to study dopamine D4 receptors both in vitro and in vivo, and has good brain penetration after subcutaneous administration. Expand
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