Lamotrigine has no antiparkinsonian activity in rat models of Parkinson's disease.
In rodent models of Parkinson's disease such as reserpinized or 6-hydroxydopamine substantia nigra lesioned rats, blockade of glutamate receptors of the NMDA (N-methyl-D-aspartate) or the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptor subtypes and concomitant treatment with L-DOPA (L-3,4-dihydroxyphenylalanine) or direct dopamine agonists restores locomotor activity and induces rotations. An alternative approach to interfere with glutamatergic transmission would involve the inhibition of glutamate release resulting in functional glutamate antagonism. The novel antiepileptic drug lamotrigine blocks the veratridine-evoked release of the excitatory transmitters L-glutamate and L-aspartate. Due to its presumed antiglutamatergic action it has been suggested that lamotrigine may be useful in the treatment of Parkinson's disease. In a preliminary open-label study in patients with Parkinson's disease some favourable effects were reported. The present study was undertaken to systematically investigate the effects of lamotrigine in rat models of Parkinson's disease. However, lamotrigine failed to exert antiparkinsonian activity in reserpinized rats when administered alone or in combination with the dopamine receptor agonist apomorphine. In rats bearing 6-hydroxydopamine lesions of the substantia nigra lamotrigine did not induce rotations when given alone and did not modify rotations induced by apomorphine or the preferential dopamine D2 receptor agonist lisuride. On the basis of these negative results it is predicted that lamotrigine will not have significant favourable effects on akinesia and rigidity in Parkinson's disease patients.
University of Tübingen, Department of Neurology, Germany.
P A
PA
Löschmann
F
F
Eblen
U
U
Wüllner
H
H
Wachtel
T
T
Kockgether
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000077213:Lamotrigine; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D012399:Rotation; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000502:physiology; D013565:Sympatholytics / Q000633:toxicity; D014227:Triazines / Q000494:pharmacology*
D000978:Antiparkinson Agents; D013565:Sympatholytics; D014227:Triazines; D012110:Reserpine; D016627:Oxidopamine; D001058:Apomorphine; D000077213:Lamotrigine