Tremorolytic effects of safinamide in animal models of drug-induced parkinsonian tremor

Samantha Podurgiel, Lyndsey E. Collins-Praino, Samantha Yohn, Patrick A. Randall, Arthur Roach, Christophe Lobianco, John D. Salamone

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Safinamide is an α-aminoamide derivative that is currently in Phase III clinical trial development as an add-on therapy to levodopa or dopamine agonists for patients with Parkinson's disease. Safinamide is a monoamine oxidase B inhibitor with additional non-dopaminergic actions. The present experiments were performed to evaluate the ability of safinamide to attenuate parkinsonian motor impairments using the tremulous jaw movement model, an animal model of parkinsonian tremor. In rats, tremulous jaw movements can be induced with dopamine (DA) antagonists, DA depletion, and cholinomimetics, and can be reversed by various antiparkinsonian drugs, including L-DOPA, DA agonists, anticholinergics and adenosine A2A antagonists. In these present experiments, tremulous jaw movements were induced with the anticholinesterase galantamine (3.0 mg/kg IP), the muscarinic agonist pilocarpine (0.5 mg/kg IP), and the dopamine D2 antagonist pimozide (1.0 mg/kg IP). Safinamide significantly reduced the number of tremulous jaw movements induced by galantamine, pilocarpine, and pimozide, with consistent effects across all three drugs at a dose range of 5.0-10.0 mg/kg. The results of this study support the use of safinamide as a treatment for parkinsonian tremor.

Original languageEnglish (US)
Pages (from-to)105-111
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume105
DOIs
StatePublished - Apr 1 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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