Effects of SIB-1508Y, a novel neuronal nicotinic acetylcholine receptor agonist, on motor behavior in parkinsonian monkeys.
Identifieur interne : 005000 ( Ncbi/Curation ); précédent : 004F99; suivant : 005001Effects of SIB-1508Y, a novel neuronal nicotinic acetylcholine receptor agonist, on motor behavior in parkinsonian monkeys.
Auteurs : J S Schneider [États-Unis] ; A. Pope-Coleman ; M. Van Velson ; F. Menzaghi ; G K LloydSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 1998.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Antiparkinson Agents (pharmacology), Dose-Response Relationship, Drug, Drug Synergism, Levodopa (pharmacokinetics), Macaca fascicularis, Male, Motor Skills (drug effects), Neurologic Examination (drug effects), Nicotinic Agonists (pharmacology), Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (physiopathology), Pyridines (pharmacology), Pyrrolidines (pharmacology), Receptors, Cholinergic (physiology), Receptors, Nicotinic (physiology).
- MESH :
- chemical , pharmacokinetics : Levodopa.
- chemical , pharmacology : Antiparkinson Agents, Nicotinic Agonists, Pyridines, Pyrrolidines.
- chemical , physiology : Receptors, Cholinergic, Receptors, Nicotinic.
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- chemically induced : Parkinson Disease, Secondary.
- drug effects : Motor Skills, Neurologic Examination.
- physiopathology : Parkinson Disease, Secondary.
- Animals, Dose-Response Relationship, Drug, Drug Synergism, Macaca fascicularis, Male.
Abstract
The potential antiparkinsonian effects of the centrally acting, subtype-selective neuronal nicotinic acetylcholine receptor agonist (S)-(-)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)-pyridine (SIB-1508Y) was assessed on motor symptoms and disability scale ratings in three monkeys previously made parkinsonian by chronic exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Compared with levodopa (L-dopa), SIB-1508Y exerted only mild antiparkinsonian effects when administered alone. Emetic effects of this drug interfered with potential therapeutic effects at higher doses. However, when a low, ineffective dose of SIB-1508Y was combined with low, ineffective doses of L-dopa, a significant clinical effect was observed. These data suggest that subtype-selective nicotinic acetylcholine receptor agonists may hold promise as antiparkinsonian agents, and when administered in combination with L-dopa may allow a reduction in the dose of L-dopa needed to achieve a significant clinical effect.
DOI: 10.1002/mds.870130405
PubMed: 9686767
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Pope-Coleman</name></author><author><name sortKey="Van Velson, M" sort="Van Velson, M" uniqKey="Van Velson M" first="M" last="Van Velson">M. Van Velson</name></author><author><name sortKey="Menzaghi, F" sort="Menzaghi, F" uniqKey="Menzaghi F" first="F" last="Menzaghi">F. 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Pope-Coleman</name></author><author><name sortKey="Van Velson, M" sort="Van Velson, M" uniqKey="Van Velson M" first="M" last="Van Velson">M. Van Velson</name></author><author><name sortKey="Menzaghi, F" sort="Menzaghi, F" uniqKey="Menzaghi F" first="F" last="Menzaghi">F. Menzaghi</name></author><author><name sortKey="Lloyd, G K" sort="Lloyd, G K" uniqKey="Lloyd G" first="G K" last="Lloyd">G K Lloyd</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="1998" type="published">1998</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Animals</term><term>Antiparkinson Agents (pharmacology)</term><term>Dose-Response Relationship, Drug</term><term>Drug Synergism</term><term>Levodopa (pharmacokinetics)</term><term>Macaca fascicularis</term><term>Male</term><term>Motor Skills (drug effects)</term><term>Neurologic Examination (drug effects)</term><term>Nicotinic Agonists (pharmacology)</term><term>Parkinson Disease, Secondary (chemically induced)</term><term>Parkinson Disease, Secondary (physiopathology)</term><term>Pyridines (pharmacology)</term><term>Pyrrolidines (pharmacology)</term><term>Receptors, Cholinergic (physiology)</term><term>Receptors, Nicotinic (physiology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiparkinson Agents</term><term>Nicotinic Agonists</term><term>Pyridines</term><term>Pyrrolidines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Receptors, Cholinergic</term><term>Receptors, Nicotinic</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Motor Skills</term><term>Neurologic Examination</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Dose-Response Relationship, Drug</term><term>Drug Synergism</term><term>Macaca fascicularis</term><term>Male</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The potential antiparkinsonian effects of the centrally acting, subtype-selective neuronal nicotinic acetylcholine receptor agonist (S)-(-)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)-pyridine (SIB-1508Y) was assessed on motor symptoms and disability scale ratings in three monkeys previously made parkinsonian by chronic exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Compared with levodopa (L-dopa), SIB-1508Y exerted only mild antiparkinsonian effects when administered alone. Emetic effects of this drug interfered with potential therapeutic effects at higher doses. However, when a low, ineffective dose of SIB-1508Y was combined with low, ineffective doses of L-dopa, a significant clinical effect was observed. These data suggest that subtype-selective nicotinic acetylcholine receptor agonists may hold promise as antiparkinsonian agents, and when administered in combination with L-dopa may allow a reduction in the dose of L-dopa needed to achieve a significant clinical effect.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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