Targeting Striatal Glutamate and Phosphodiesterases to Control L-DOPA-Induced Dyskinesia.

ABSTRACT: A large body of work during the past several decades has been focused on therapeutic strategies to control L-DOPA-induced dyskinesias (LIDs), common motor complications of long-term L-DOPA therapy in Parkinson's disease (PD). Yet, LIDs remain a clinical challenge for the management of patients with advanced disease. Glutamatergic dysregulation of striatal projection neurons (SPNs) appears to be a key contributor to altered motor responses to L-DOPA. Targeting striatal hyperactivity at the glutamatergic neurotransmission level led to significant preclinical and clinical trials of a variety of antiglutamatergic agents. In fact, the only FDA-approved treatment for LIDs is amantadine, a drug with NMDAR antagonistic actions. Still, novel agents with improved pharmacological profiles are needed

SUBMITTER: Kochoian BA 

PROVIDER: S-EPMC10706484 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature