Synergistic interactions between COMT-/MAO-inhibitors and L-Dopa in MPTP-treated mice
Identifieur interne : 002278 ( Main/Exploration ); précédent : 002277; suivant : 002279Synergistic interactions between COMT-/MAO-inhibitors and L-Dopa in MPTP-treated mice
Auteurs : A. Fredriksson ; T. Archer [Suède]Source :
- Journal of Neural Transmission / General Section JNT [ 0300-9564 ] ; 1995-02-01.
Abstract
Summary: Four experiments were performed to investigate the anti-akinesia effects of combining a sub-threshold dose (5mg/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-Deprenyl, by itself, stimulated motor activity following injection of L-Dopa. Marked dopamine (DA) depletions in the striatum of MPTP-treated mice were evident. The present results demonstrate that the effects of the COMT/MAO inhibitors in combination, and in conjunction with L-Dopa (at a dose that was without effect by itself), were well in excess of a summation of their individual effects. It was concluded therefore that a synergism of the restorative, anti-akinesic action of these compounds in MPTP-treated mice could offer a broader therapeutic spectrum in the treatment of Parkinson's disorder.
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DOI: 10.1007/BF01276562
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Archer</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:1804D1C27E122FB2CF18E88A341B7D1BB65D5022</idno><date when="1995" year="1995">1995</date><idno type="doi">10.1007/BF01276562</idno><idno type="url">https://api.istex.fr/document/1804D1C27E122FB2CF18E88A341B7D1BB65D5022/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001D03</idno><idno type="wicri:Area/Main/Curation">001A28</idno><idno type="wicri:Area/Main/Exploration">002278</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Synergistic interactions between COMT-/MAO-inhibitors and L-Dopa in MPTP-treated mice</title><author><name sortKey="Fredriksson, A" sort="Fredriksson, A" uniqKey="Fredriksson A" first="A." last="Fredriksson">A. Fredriksson</name><affiliation><wicri:noCountry code="subField">Uppsala</wicri:noCountry></affiliation></author><author><name sortKey="Archer, T" sort="Archer, T" uniqKey="Archer T" first="T." last="Archer">T. Archer</name><affiliation wicri:level="4"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Psychology, Göteborg University, Göteborg</wicri:regionArea><orgName type="university">Université de Göteborg</orgName><placeName><settlement type="city">Göteborg</settlement><region nuts="1">Götaland</region><region nuts="1">Suède occidentale</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Neural Transmission / General Section JNT</title><title level="j" type="abbrev">J. Neural Transmission</title><idno type="ISSN">0300-9564</idno><idno type="eISSN">1435-1463</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Vienna</pubPlace><date type="published" when="1995-02-01">1995-02-01</date><biblScope unit="volume">102</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="19">19</biblScope><biblScope unit="page" to="34">34</biblScope></imprint><idno type="ISSN">0300-9564</idno></series><idno type="istex">1804D1C27E122FB2CF18E88A341B7D1BB65D5022</idno><idno type="DOI">10.1007/BF01276562</idno><idno type="ArticleID">Art2</idno><idno type="ArticleID">BF01276562</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0300-9564</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Summary: Four experiments were performed to investigate the anti-akinesia effects of combining a sub-threshold dose (5mg/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-Deprenyl, by itself, stimulated motor activity following injection of L-Dopa. Marked dopamine (DA) depletions in the striatum of MPTP-treated mice were evident. The present results demonstrate that the effects of the COMT/MAO inhibitors in combination, and in conjunction with L-Dopa (at a dose that was without effect by itself), were well in excess of a summation of their individual effects. It was concluded therefore that a synergism of the restorative, anti-akinesic action of these compounds in MPTP-treated mice could offer a broader therapeutic spectrum in the treatment of Parkinson's disorder.</div></front></TEI><affiliations><list><country><li>Suède</li></country><region><li>Götaland</li><li>Suède occidentale</li></region><settlement><li>Göteborg</li></settlement><orgName><li>Université de Göteborg</li></orgName></list><tree><noCountry><name sortKey="Fredriksson, A" sort="Fredriksson, A" uniqKey="Fredriksson A" first="A." last="Fredriksson">A. Fredriksson</name></noCountry><country name="Suède"><region name="Götaland"><name sortKey="Archer, T" sort="Archer, T" uniqKey="Archer T" first="T." last="Archer">T. Archer</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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