MapLight Therapeutics is advancing understanding and creating novel therapies for Parkinson’s.

Circuit Approach Elucidates Novel Role for 5-HT2C Antagonists Parkinson’s

  • Serotonergic projections from the dorsal raphe innervate motor control regions
  • Circuit Dysfunction leads to motor and non-motor symptoms in Parkinson’s
  • 5-HT2C antagonists have potential to normalize circuit function

Pre-Clinical and Clinical Evidence Supporting Anti-Parkinsonian Utility

  • 5-HT2C receptor antagonists enhance the behavioral response to dopamine receptor agonists in the 6-hydroxydopamine-lesioned rat (Fox and Brotchie)
  • A 5-HT2C antagonist reversed bradykinesia in an optogenetic circuit model of PD and in a 6-OHDA mouse model (Internal).
  • In a small patient study, a non-specific 5-HT2 (A, B & C) receptor antagonist improved akinesia and gait (Henderson) • Antidepressants with 5-HT2c antagonist activity have been reported to slow PD progression (Avila)
  • Selective serotonin re-uptake inhibitors (SSRIs) may worsen PD symptoms at higher doses (Richard) • SSRI-induced motor deficits can be reversed by 5-HT2C antagonism and potentiates anxiolytic effects of SSRIs (Demireva)

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