PMID: 8785021Jan 1, 1995

Synergistic interactions between COMT-/MAO-inhibitors and L-Dopa in MPTP-treated mice

Journal of Neural Transmission. General Section
A Fredriksson, T Archer

Abstract

Four experiments were performed to investigate the anti-akinesia effects of combining a sub-threshold dose (5 mg/kg, s.c.) of L-Dopa with different doses and combinations of COMT and MAO inhibitors upon the hypokinesia observed in MPTP-treated mice. Ro 40-7592 (1 and 3 mg/kg, s.c.), a novel COMT inhibitor, 60 min before L-Dopa reinstated both locomotion and rearing during a 2-hr interval after L-Dopa in MPTP mice; control mice were unaffected. The combination of Ro 40-7592 (3 mg/kg, s.c.) and pargyline (5 mg/kg, s.c.), a MAO inhibitor, with L-Dopa produced increases in both the peak effect and duration of action indicating a distinct potentiation of the effects of Ro 40-7592 by pargyline. L-Deprenyl, a MAOB inhibitor, together with L-Dopa, restored locomotion and rearing behaviour at all three doses applied (1, 3 and 10 mg/kg, s.c.); in control mice, motor activity was stimulated at the higher doses (3 and 10 mg/kg, s.c.), independent of L-Dopa administration. Combining L-Deprenyl (3 mg/kg, s.c.) with Ro 40-7592 (3 mg/kg, s.c.) one hr before L-Dopa to MPTP mice potentiated the restorative effects of each compound by itself, although no increase in peak effect was obtained. In the control mice, L-Deprenyl plus Ro 40-7592 or L-De...Continue Reading

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Citations

Apr 29, 1998·Biulleten' eksperimental'noĭ biologii i meditsiny·E A BudyginP T Männistö
Jun 22, 2006·Neurotoxicity Research·T Archer, A Fredriksson
Oct 9, 1998·Journal of Neuroscience Methods·G RozasJ L Labandeira-García
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Mar 15, 2001·Parkinsonism & Related Disorders·A FredrikssonT Archer
Jul 25, 2013·Neuroscience Letters·Rachanee ChanasongSutisa Nudmamud-Thanoi
Dec 11, 2007·The Journal of Pharmacology and Experimental Therapeutics·Eric C K Siu, Rachel F Tyndale
Nov 21, 2019·Expert Opinion on Drug Discovery·Kalliopi MoschovouAntreas Afantitis

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Behavior, Animal
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

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