A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats

  title={A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats},
  author={Kaitlin E. Browman and Peter Curzon and Jia Bao Pan and Angela L Molesky and Victoria A. Komater and Michael W. Decker and Jorge D. Brioni and Robert B. Moreland and Gerard B. Fox},
  journal={Pharmacology Biochemistry and Behavior},

Selective dopamine D4 receptor agonist (A-412997) improves cognitive performance and stimulates motor activity without influencing reward-related behaviour in rat

Comparing the effects of a selective D4 receptor agonist, A-412997, with methylphenidate or amphetamine in preclinical models of efficacy versus abuse liability suggests that selective activation of the D4 receptors may represent a target for the treatment of attention deficit hyperactivity disorder without the potential drug abuse liability associated with current psychostimulant therapies.

Dopamine D4 receptor stimulation contributes to novel object recognition: Relevance to cognitive impairment in schizophrenia

D4 receptor agonism has a beneficial effect on novel object recognition in sub-chronic PCP-treated rats and augments the cognitive enhancing efficacy of an atypical antipsychotic drug that lacks affinity for the D4 receptor, lurasidone.

Dopamine D4 Receptor-Selective Compounds Reveal Structure–Activity Relationships that Engender Agonist Efficacy

A series of eighteen novel ligands based on the classical D4R agonist A-412997 are reported, highlighting receptor–ligand interactions that control efficacy at D2-like receptors and may provide insights into targeted drug discovery, leading to a better understanding of the role of D4Rs in neuropsychiatric disorders.

Behavioral and neurophysiological effects of Ro 10-5824, a dopamine D4 receptor partial agonist, in common marmosets

Activation of D4R by Ro 10-5824 improves the success rate in the ORD task and increases baseline gamma band activity in the frontal cortex without affecting locomotion in common marmosets, highlighting the role of D 4R in gamma oscillations of non-human primates.

PD168077, a D4 receptor agonist, reverses object recognition deficits in rats: potential role for D4 receptor mechanisms in improving cognitive dysfunction in schizophrenia

The results suggest that D4 receptor activation can improve cognitive dysfunction in an animal model relevant to schizophrenia.

Enhancement of gamma activity after selective activation of dopamine D4 receptors in freely moving rats and in a neurodevelopmental model of schizophrenia

The involvement of D4R in cortical gamma oscillations in vivo is demonstrated and this receptor is identified as potential target for pharmacological treatment of cognitive deficits.



Effects of dopamine D4 receptor-selective antagonists on motor hyperactivity in rats with neonatal 6-hydroxydopamine lesions

Motor hyperactivity in this ADHD model was selectively antagonized by three of four dopamine D4 receptor antagonists evaluated, encouraging clinical assessment of D4 antagonists in patients with ADHD.

The effects of a selective D4 dopamine receptor antagonist (L-745,870) in acutely psychotic inpatients with schizophrenia. D4 Dopamine Antagonist Group.

The selective D4 dopamine receptor antagonist L-745,870 was ineffective as an antipsychotic for the treatment of neuroleptic responsive inpatients with acute schizophrenia.

The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder

Results from a combination of genetic and pharmacological approaches demonstrate that D4R signaling is essential for the expression of juvenile hyperactivity and impaired behavioral inhibition, relevant features present in this ADHD-like mouse model.

Two Novel and Selective Nonimidazole H3 Receptor Antagonists A-304121 and A-317920: II. In Vivo Behavioral and Neurophysiological Characterization

  • G. FoxJ. Pan A. Hancock
  • Biology, Chemistry
    Journal of Pharmacology and Experimental Therapeutics
  • 2003
A-304121 and A-317920 represent a series of novel, H3R-selective piperazine amides that enhance cognition in vivo, which could offer advantages over existing H3 R antagonists or cognition-enhancing agents.