D1 Agonist Improved Movement of Parkinsonian Nonhuman Primates with Limited Dyskinesia Side Effects

ACS Chem Neurosci. 2020 Feb 19;11(4):560-566. doi: 10.1021/acschemneuro.9b00589. Epub 2020 Feb 6.

Abstract

Parkinson's disease is a progressive neurodegenerative disease characterized by striatal dopaminergic loss. L-DOPA treatment replaces lost dopamine and enables motor function; however, eventually, fluctuating efficacy and side effects associated with its use become challenging for many patients. Here, we demonstrate, in a clinically translatable nonhuman primate model of parkinsonian motor symptoms, that treatment with the partial D1 receptor agonist CVL-751, formerly known as PF-06649751, is just as effective as L-DOPA in enabling movement and reducing disability. Importantly, CVL-751 efficacy is observed with less of the concomitant dyskinesia side effect associated with L-DOPA treatment. Data presented suggest that partial D1 agonists may be an effective and important treatment strategy for the management of Parkinson's patients.

Keywords: D1 receptor agonist; Parkinson’s disease; dyskinesia; nonhuman primate.

MeSH terms

  • Animals
  • Antiparkinson Agents / pharmacology
  • Corpus Striatum / drug effects
  • Dopamine / pharmacology
  • Dopamine Agonists / pharmacology*
  • Dyskinesia, Drug-Induced / drug therapy
  • Motor Activity / drug effects*
  • Neurodegenerative Diseases / drug therapy*
  • Oxidopamine / pharmacology
  • Parkinson Disease / drug therapy
  • Parkinsonian Disorders / drug therapy*
  • Rats

Substances

  • Antiparkinson Agents
  • Dopamine Agonists
  • Oxidopamine
  • Dopamine