A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia

  title={A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia},
  author={Qiwen Mu and Kevin Johnson and Paul Simon Morgan and Emily L. Grenesko and Christine E. Molnar and Berry S. Anderson and Ziad Nahas and F. Andrew Kozel and Samet Kose and Michael B. Knable and Prabhavathi Fernandes and David E. Nichols and Richard B. Mailman and Mark S. George},
  journal={Schizophrenia Research},

A proof-of-concept, randomized controlled trial of DAR-0100A, a dopamine-1 receptor agonist, for cognitive enhancement in schizophrenia

It is suggested that low doses of D1 agonists that do not result in measureable occupancy of the D1R do not reliably improve cognition in SCZ, unlike the observations in NHP.

Multiple dopamine receptors mediate the discriminative stimulus effects of dihydrexidine in rats

Determinations of activity at second messenger systems revealed that DHX functioned as a full agonist at D3 receptors and a partial agonists at D2 receptors in vitro, suggesting that both D1 and D2/D3 receptors mediate the discriminative stimulus effects of DHX.

Baseline Perfusion Alterations Due to Acute Application of Quetiapine and Pramipexole in Healthy Adults

It is found that quetiapine reduced perfusion in the occipital and bilateral cerebellar cortex relative to placebo and pramipexole differentially modulate regional baseline cerebral blood flow.

Novel Dopamine Therapeutics for Cognitive Deficits in Schizophrenia

Pharmacokinetics of ASP4345 from Single Ascending-Dose and Multiple Ascending-Dose Phase I Studies

The pharmacokinetics of ASP4345 suggest that single daily dosing is appropriate for ASP 4345, and the concentration of AS4345 in cerebrospinal fluid compared to free drug concentrations in plasma provides evidence of penetration ofAS4345 into the brain.

Characterization of PF-6142, a Novel, Non-Catecholamine Dopamine Receptor D1 Agonist, in Murine and Nonhuman Primate Models of Dopaminergic Activation

PF-6142 improved performance in rodent models of NMDA receptor antagonist-induced cognitive dysfunction, and reversed ketamine-induced deficits in NHP performing the spatial delayed recognition task, and did not alter the efficacy of risperidone in assays predictive of antipsychotic-like effect in rodents including pre-pulse inhibition and conditioned avoidance responding.



Prefrontal Dopamine D1 Receptors and Working Memory in Schizophrenia

Findings confirm that alteration of DLPFC D1 receptor transmission is involved in working memory deficits presented by patients with schizophrenia.

Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET

Although no differences were observed in the striatum relative to control subjects, binding of radioligand to D1R was reduced in the prefrontal cortex of schizophrenics, and this reduction was related to the severity of the negative symptoms and to poor performance in the Wisconsin Card Sorting Test.

Dihydrexidine--the first full dopamine D1 receptor agonist.

An updated overview of the pharmacology of dihydrexidine is provided and possible clinical utility of dopamine D(1) receptor agonists in various central nervous system disorders is discussed.

Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys

Results underscore the importance of DA D1 mechanisms in cognitive function, and provide functional evidence of DA system degeneration in aged monkeys, suggesting that excessive D1 stimulation may be deleterious to cognitive function.

PET study of D(1) dopamine receptor binding in neuroleptic-naive patients with schizophrenia.

These results do not replicate previous postmortem and PET findings of altered central dopamine D(1) receptor binding in schizophrenia and the finding of a positive correlation between frontal D( 1) binding and scores on the negative symptom subscale of the BPRS is contrary to a previously reported finding ofA negative correlation.

An increase in [3H]SCH23390 binding in the cerebral cortex of postmortem brains of chronic schizophrenics

The results suggest that there are changes in dopaminergic transmission through the D1 receptors in the parieto-temporal cortex of schizophrenia, and that the altered functions are involved in the pathophysiology of the disease.