Cholinergic manipulation of motor disability and L-DOPA-induced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets. 2014

M J Jackson, and T Swart, and R K B Pearce, and P Jenner

Anti-cholinergic drugs are used in the treatment of Parkinson’s disease (PD) and they can improve motor disability in some patients and may alter the expression of dyskinesia. We report the effects of anticholinergic and pro-cholinergic agents administered alone and combined with L-DOPA, on motor function in 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets. Administration of atropine to MPTP-treated marmosets, not previously exposed to L-DOPA, improved motor disability but this did not occur with other centrally acting anti-cholinergics. Motor disability was worsened by centrally acting pro-cholinergics. However, neither peripherally acting anti- nor pro-cholinergics produced any effect on motor disability or dyskinesia. In MPTP-treated marmosets previously primed with L-DOPA to exhibit dyskinesia, acute L-DOPA challenge induced both chorea and dystonia. In these animals, centrally acting anti-cholinergics including atropine and trihexyphenidyl reversed motor deficits, but induced chorea. Combined with L-DOPA, both centrally and peripherally acting anti-cholinergics reduced peak locomotor activity and produced more chorea than dystonia compared to L-DOPA alone. Centrally acting pro-cholinergics decreased locomotor activity, worsened motor disability and induced dystonia. Co-administered with L-DOPA, pro-cholinergics reduced locomotor activity and decreased chorea while increasing dystonia compared with L-DOPA alone. In conclusion, anti-cholinergics can increase chorea with and without L-DOPA but improve motor disability. Pro-cholinergics decrease the proportion of chorea when combined with L-DOPA, increase motor disability and antagonise L-DOPA’s effectiveness. These data suggest that there may be a case for revisiting the use of anti-cholinergic drugs in the treatment of PD.

UI MeSH Term Description Entries
D007980 Levodopa The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. L-Dopa,3-Hydroxy-L-tyrosine,Dopaflex,Dopar,L-3,4-Dihydroxyphenylalanine,Larodopa,Levopa,3 Hydroxy L tyrosine,L 3,4 Dihydroxyphenylalanine,L Dopa
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D002144 Callithrix A genus of the subfamily CALLITRICHINAE occurring in forests of Brazil and Bolivia and containing seventeen species. Callithrix jacchus,Hapale,Marmoset, Common,Marmoset, Short-Tusked,Marmosets,Common Marmoset,Common Marmosets,Marmoset,Marmoset, Short Tusked,Short-Tusked Marmoset,Short-Tusked Marmosets
D002230 Carbidopa An inhibitor of DOPA DECARBOXYLASE that prevents conversion of LEVODOPA to dopamine. It is used in PARKINSON DISEASE to reduce peripheral adverse effects of LEVODOPA. It has no anti-parkinson activity by itself. Methyldopahydrazine,Carbidopa, (R)-Isomer,Carbidopa, (S)-Isomer,Lodosin,Lodosyn,MK-485,MK-486,MK 485,MK 486,MK485,MK486
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004409 Dyskinesia, Drug-Induced Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199) Dyskinesia, Medication-Induced,Medication-Induced Dyskinesia,Drug-Induced Dyskinesia,Drug-Induced Dyskinesias,Dyskinesia, Drug Induced,Dyskinesia, Medication Induced,Dyskinesias, Drug-Induced,Dyskinesias, Medication-Induced,Medication Induced Dyskinesia,Medication-Induced Dyskinesias
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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