TY - JOUR
T1 - Tremorolytic effects of safinamide in animal models of drug-induced parkinsonian tremor
AU - Podurgiel, Samantha
AU - Collins-Praino, Lyndsey E.
AU - Yohn, Samantha
AU - Randall, Patrick A.
AU - Roach, Arthur
AU - Lobianco, Christophe
AU - Salamone, John D.
N1 - Funding Information:
This work was supported by grants to J.S. from Merck Serono , and the University of Connecticut Research Foundation . Many thanks to Hector Contreras for his assistance with the data analyses.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.pbb.2013.01.015
DO - 10.1016/j.pbb.2013.01.015
M3 - Article
C2 - 23360954
AN - SCOPUS:84874414183
SN - 0091-3057
VL - 105
SP - 105
EP - 111
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
ER -