Modification of levodopa responses by deprenyl (selegiline): an electrophysiological and behavioral study in the rat relevant to Parkinson's disease.
From using in vitro intracellular recordings from mesencephalic neurons and monoamine-depleted rats, we report that the functions of levodopa in the brain are greatly enhanced and prolonged by high doses of the monoamine oxidase (MAO) inhibitor deprenyl. Dopaminergic neurons were hyperpolarized and inhibited by levodopa application. These effects of levodopa were largely potentiated by pretreatment with nonselective doses of deprenyl. Furthermore, when locomotor activity induced by levodopa was examined on a rodent model of Parkinson's disease, pretreatment of the animals with nonselective doses of deprenyl caused an enhancement of the antiparkinsonian action of levodopa. The great increase in levodopa responses by deprenyl suggests a likely therapeutic use of this dopamine precursor with a higher dosage of the MAO inhibitor, to reduce effectively the daily levodopa requirements in Parkinson's disease patients.
Mercuri
N B
NB
IRCCS Santa Lucia and Clinica Neurologica, University of Tor Vergata, Rome, Italy.
Scarponi
M
M
Federici
M
M
Bonci
A
A
Siniscalchi
A
A
Bernardi
G
G
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D004594:Electrophysiology; D007274:Injections, Intraperitoneal; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*
D000978:Antiparkinson Agents; D012642:Selegiline; D007980:Levodopa