Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity

Life Sci. 1999;64(15):1275-85. doi: 10.1016/s0024-3205(99)00062-4.


Pramipexole, a novel non-ergoline dopamine (DA) agonist, has been applied successfully for treatment of Parkinson's disease (PD). We report here that pramipexole can protect dopaminergic cell line Mes23.5 against dopamine- and levodopa-induced cytotoxicity possibly through a mechanism related to antioxidant activity. In the MES 23.5 cultures, DA and L-DOPA induce a dose- and time-dependent cytotoxicity, as determined by tetrazolium salt and trypan blue assays. Furthermore, an in situ terminal deoxynucleotidyl transferase assay demonstrates that DA-induced cell death is apoptotic. Pretreatment with pramipexole in a concentration range (4-100 microM) significantly attenuates DA- or L-DOPA-induced cytotoxicity and apoptosis, an action which is not blocked by D3 antagonist U-99194 A or D2 antagonist raclopride. Pramipexole also protects MES 23.5 cells from hydrogen peroxide-induced cytotoxicity in a dose-dependent manner. In cell-free system, pramipexole can effectively inhibit the formation of melanin, an end product resulting from DA or L-DOPA oxidation. These results indicate that pramipexole exerts its neuroprotective effect possibly through a mechanism, which is independent of DA receptors but related to antioxidation or scavenging of free radicals (e.g. hydrogen peroxide). As a direct DA agonist and potentially neuroprotective agent, pramipexole remains attractive in the treatment of PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzothiazoles
  • Cell Line
  • Cell Survival / drug effects
  • Dopamine / toxicity*
  • Dopamine Agonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Glioma
  • Hybrid Cells
  • Kinetics
  • Levodopa / toxicity*
  • Neuroblastoma
  • Neuroprotective Agents / pharmacology*
  • Pramipexole
  • Thiazoles / pharmacology*


  • Benzothiazoles
  • Dopamine Agonists
  • Neuroprotective Agents
  • Thiazoles
  • Levodopa
  • Pramipexole
  • Dopamine