A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia

  title={A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia},
  author={Mark S. George and Christine E. Molnar and Emily L. Grenesko and Berry S. Anderson and Qiwen Mu and Kevin Johnson and Ziad Nahas and Michael B. Knable and Prabhavathi Fernandes and Jorge J Juncos and Xuemei Huang and David E. Nichols and Richard B. Mailman},
  journal={Schizophrenia Research},

Effects of the D1 Dopamine Receptor Agonist Dihydrexidine (DAR-0100A) on Working Memory in Schizotypal Personality Disorder

Findings lend further clinical support to the potential of D1 receptor agonists to treat schizophrenia-spectrum working memory impairments, and suggest a need for further studies with larger group sizes, serum DAR-0100A levels, and a more comprehensive neuropsychological battery.

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.

A proof-of-principle study of the effect of combined haloperidol and levodopa administration on working memory-related brain activation in humans

This preliminary study provides initial evidence for combined L-dopa/haloperidol modulation in cognition-related brain areas and networks, which is relevant for the treatment of cognitive impairments in mental illness.

The D 1 /D 5 dopamine partial agonist PF-06412562 in advanced­ stage Parkinson’s disease: a feasibility study

This study provides the feasibility for future safety and efficacy studies in this population with unmet needs by comparing standard-of-care carbidopa/levodopa with a selective D 1 /D 5 dopamine receptor partial agonist.

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.

The D1/D5 Dopamine Partial Agonist PF-06412562 in Advanced-Stage Parkinson's Disease: A Feasibility Study.

PF-06412562 was tolerated in advPD patients and provides the feasibility for future safety and efficacy studies in this population with unmet needs.

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.

Characterization of in vivo Pharmacokinetic Properties of the Dopamine D1 Receptor Agonist DAR-0100A in Nonhuman Primates Using PET with [11C] NNC112 and [11C] Raclopride

Data suggest that at doses likely to be administered to patients, occupancy will not be detectable with [11C] NNC112 PET and binding of DAR-0100A to D2 will be negligible, the first demonstration with PET of a significant occupancy by a full D1 agonist in vivo.

Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents

An update and critical review of the pharmacology and clinical profiles of current antipsychotic drugs and drugs acting on novel targets with potential to be therapeutic agents in the future is provided.



Effects of the Full Dopamine Dl Receptor Agonist Dihydrexidine in Parkinson's Disease

Preliminary data suggest that dihydrexidine has a marginal therapeutic window for providing an anti-parkinsonian effect, although it remains uncertain how much of this effect is attributable to pure Dl receptor stimulation.

Lack of apparent antipsychotic effect of the D1-dopamine recepotr antagonist SCH39166 in acutely ill schizophrenic patients

The result of the study does not support the prediction that selective D1 dopamine receptor antagonism will produce antipsychotic effects in schizophrenia.

A common action of clozapine, haloperidol, and remoxipride on D1- and D2-dopaminergic receptors in the primate cerebral cortex.

  • M. LidowP. Goldman-Rakic
  • Psychology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
Chronic treatment with clozapine, haloperidol, and remoxipride up-regulates D2 receptors in specific cortical areas of the rhesus monkey frontal, parietal, temporal, and occipital lobes, raising the possibility that down-regulation of D1 receptors in prefrontal and temporal cortex may be an important component of the therapeutic response to neuroleptic drugs.

ABT‐431, a D1 receptor agonist prodrug, has efficacy in Parkinson's disease

ABT‐431 is the first dopamine D1 receptor agonist to demonstrate a full antiparkinsonian effect in patients with Parkinson's disease, and these preliminary findings suggest that it may exhibit a reduced tendency to provoke dyskinesia.

The D1 Agonist Dihydrexidine Releases Acetylcholine and Improves Cognition in Rats

Results provided support for the hypothesis that DHX improves cognitive performance as a consequence of ACh release in relevant brain regions, and D1 agonists may have novel therapeutic potential in the treatment of dementia.

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.

Down-regulation of the D1 and D5 dopamine receptors in the primate prefrontal cortex by chronic treatment with antipsychotic drugs.

A reduction in the levels of prefrontal cortical dopamine receptors of the D1 class may be an obligatory consequence of D2 receptor antagonism and thus may be a pharmacological property of antipsychotic drugs.

Differential effects of the D1-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia

The results of the present study do not support the hypothesis that D1-dopamine antagonists are clinically effective antipsychotics in schizophrenia, considering the fact that SCH 39166 had no effect on positive symptoms.