Tremorolytic effects of safinamide in animal models of drug-induced parkinsonian tremor.
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 (3.0mg/kg IP), the muscarinic agonist pilocarpine (0.5mg/kg IP), and the dopamine D2 antagonist pimozide (1.0mg/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 5.0-10.0mg/kg. The results of this study support the use of safinamide as a treatment for parkinsonian tremor.
Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
Samantha
S
Podurgiel
Lyndsey E
LE
Collins-Praino
Samantha
S
Yohn
Patrick A
PA
Randall
Arthur
A
Roach
Christophe
C
Lobianco
John D
JD
Salamone
D000409:Alanine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001596:Benzylamines / Q000009:adverse effects*; D018491:Dopamine Agonists / Q000009:adverse effects*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018721:Muscarinic Agonists / Q000009:adverse effects; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000188:drug therapy; D010862:Pilocarpine / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014202:Tremor / Q000139:chemically induced* / Q000188:drug therapy
D000978:Antiparkinson Agents; D001596:Benzylamines; D018491:Dopamine Agonists; D018721:Muscarinic Agonists; D010862:Pilocarpine; C092797:safinamide; D000409:Alanine