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

Mark S. George, Christine E. Molnar, Emily L. Grenesko, Berry Anderson, Qiwen Mu, Kevin Johnson, Ziad Nahas, Michael Knable, Prabhavathi Fernandes, Jorge Juncos, Xuemei Huang, David E. Nichols, Richard Mailman

Research output: Contribution to journalArticle

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Abstract

The potential of dopamine D1 receptor agonists to have beneficial effects on cognitive function has been suggested by a body of preclinical evidence. We now report the use of dihydrexidine (DAR-0100), the first full D1 agonist, in a pilot study assessing single low dose safety and tolerability in patients with schizophrenia. A within-subject cross-over design was used in 20 adults (18-65 years) with SCID-IV diagnosed schizophrenia. Subjects were outpatients with a moderate level of residual negative symptoms, and were on stable dosing of non-D1-blocking antipsychotic drugs. Following screening, subjects were hospitalized for 48 h, and at 0800 h each morning scanned on a 3 T MRI scanner for resting brain perfusion, followed by a Blood Oxygen Level Dependent (BOLD) fMRI scan during an N-Back working memory task. They then received 20 mg subcutaneously (SC) of dihydrexidine or placebo over 15 min, followed by 45 min of intermittent MRI scans of perfusion and BOLD activity during the working memory task. Blood was drawn for serum drug levels and subjects were evaluated for clinical and cognitive changes. The procedure was repeated using the opposite challenge 2 days later. Dihydrexidine was well tolerated with no serious adverse events although three subjects had mild dizziness and five subjects experienced nausea. There was no significant effect of drug on clinical interview ratings or delayed (afternoon) neuropsychological performance. No medication interactions were seen. Thus, a single subcutaneous dose of dihydrexidine is tolerated and safe in patients with schizophrenia and does not produce delayed clinical or neuropsychological improvements.

Original languageEnglish (US)
Pages (from-to)42-50
Number of pages9
JournalSchizophrenia Research
Volume93
Issue number1-3
DOIs
StatePublished - Jul 1 2007

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Dopamine Agonists
Schizophrenia
Short-Term Memory
Perfusion
Magnetic Resonance Imaging
Oxygen
Dopamine D1 Receptors
Dizziness
Pharmaceutical Preparations
Cross-Over Studies
Cognition
Nausea
Antipsychotic Agents
Outpatients
Placebos
Interviews
Safety
dihydrexidine
Brain
Serum

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

George, Mark S. ; Molnar, Christine E. ; Grenesko, Emily L. ; Anderson, Berry ; Mu, Qiwen ; Johnson, Kevin ; Nahas, Ziad ; Knable, Michael ; Fernandes, Prabhavathi ; Juncos, Jorge ; Huang, Xuemei ; Nichols, David E. ; Mailman, Richard. / A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia. In: Schizophrenia Research. 2007 ; Vol. 93, No. 1-3. pp. 42-50.
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George, MS, Molnar, CE, Grenesko, EL, Anderson, B, Mu, Q, Johnson, K, Nahas, Z, Knable, M, Fernandes, P, Juncos, J, Huang, X, Nichols, DE & Mailman, R 2007, 'A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia', Schizophrenia Research, vol. 93, no. 1-3, pp. 42-50. https://doi.org/10.1016/j.schres.2007.03.011

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

In: Schizophrenia Research, Vol. 93, No. 1-3, 01.07.2007, p. 42-50.

Research output: Contribution to journalArticle

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