dc.contributor.author | Iravani, Mahmoud M. | |
dc.contributor.author | Tayarani-Binazir, Kayhan | |
dc.contributor.author | Chu, Wing B. | |
dc.contributor.author | Jackson, Michael J. | |
dc.contributor.author | Jenner, Peter | |
dc.date.accessioned | 2013-12-17T13:30:12Z | |
dc.date.available | 2013-12-17T13:30:12Z | |
dc.date.issued | 2006-12 | |
dc.identifier.citation | Iravani , M M , Tayarani-Binazir , K , Chu , W B , Jackson , M J & Jenner , P 2006 , ' In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with\increased motor disability ' , Journal of Pharmacology and Experimental Therapeutics , vol. 319 , no. 3 , pp. 1225-1234 . https://doi.org/10.1124/jpet.106.110429 | |
dc.identifier.issn | 0022-3565 | |
dc.identifier.other | ORCID: /0000-0002-4905-9682/work/32997583 | |
dc.identifier.uri | http://hdl.handle.net/2299/12374 | |
dc.description.abstract | 5-Hydroxytryptamine 1a (5-HT1a) receptor agonists, such as sarizotan and tandospirone, are reported to reduce levodopainduced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques and in Parkinson's disease without worsening motor disability. However, these compounds are not specific for 5-HT1a receptors and also possess dopamine antagonist actions. We now report on the effects of (2R)-(+)-8-hydroxy-2-(di-n-propylamino) tetralin [(R)-(+)-8-OHDPAT], a selective 5-HT1a agonist lacking dopaminergic activity, on motor disability and dyskinesia (chorea and dystonia) in levodopa-primed MPTP-treated common marmosets. Administration of (R)-(+)-8-OHDPAT (0.2, 0.6, and 2.0 mg/ kg s.c), in conjunction with levodopa/ carbidopa (12.5 mg/ kg each p.o.) to levodopa-primed animals, dose-dependently reduced levodopa-induced chorea but did not affect dystonic movements. However, (R)-(+)-8-OHDPAT treatment also reduced locomotor activity and the reversal of motor disability. Administration of (R)-(+)-8-OHDPAT alone had no effects of motor behaviors. The effects of (R)-(+)-8-OHDPAT on levodopa-induced motor behaviors were antagonized by the 5-HT1a receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]N-2-pyridinylcyclohexanecarboxamide maleate (WAY-100635) (1.0 mg/ kg s. c.). Administration of (R)-(+)-8-OHDPAT (0.6 mg/ kg s. c.) also reduced chorea produced by the administration of the D-2/D-3 dopamine receptor agonist pramipexole (0.06 mg/ kg p. o.) to levodopa-primed MPTP-treated animals. However, again the increase in locomotor activity and reversal of motor disability produced by pramipexole were also inhibited. These data suggest that selective 5-HT1a agonists do not provide an effective means of suppressing levodopa-induced dyskinesia, except with worsening of parkinsonism. | en |
dc.format.extent | 10 | |
dc.language.iso | eng | |
dc.relation.ispartof | Journal of Pharmacology and Experimental Therapeutics | |
dc.subject | 5-HT1A RECEPTOR AGONIST | |
dc.subject | STRIATAL DOPAMINE RELEASE | |
dc.subject | PARKINSONS-DISEASE | |
dc.subject | RAT STRIATUM | |
dc.subject | IN-VIVO | |
dc.subject | 8-OH-DPAT | |
dc.subject | SARIZOTAN | |
dc.subject | BRAIN | |
dc.subject | ANTAGONISTS | |
dc.subject | EXPRESSION | |
dc.title | In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with\increased motor disability | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Basic and Clinical Science Unit | |
dc.contributor.institution | Centre for Health Services and Clinical Research | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1124/jpet.106.110429 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |