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Dyskinesias in normal squirrel monkeys induced by nomifensine and levodopa.
Neuropharmacology. 2005 Mar; 48(3):398-405.N

Abstract

The mechanisms underlying levodopa-induced dyskinesias are unclear. They might involve impairment of the buffering capacity for dopamine, resulting from loss of nigral dopaminergic cells and the subsequent degeneration of their terminals in striatum. This study investigated the role of striatal buffering in the development of dyskinesias. We used nomifensine, a selective dopamine reuptake blocker, to pharmacologically impair presynaptic buffering capacity in normal squirrel monkeys. Dyskinesias were assessed at 30-min intervals for 4 h after twice-daily treatment with drug. As previously reported by our group, animals receiving levodopa alone (15 mg/kg) exhibited dyskinetic behavior. Treatment with nomifensine alone (3 mg/kg) also induced dyskinesias. Furthermore, combining levodopa with nomifensine significantly increased dyskinesias. Over 4 weeks of treatment, the animals developed tolerance to the dyskinesia-inducing effect of nomifensine. The development of tolerance was prevented by concurrent treatment with levodopa. These results show that impairing buffering by preventing dopamine reuptake can induce dyskinesias and can also augment levodopa-induced dyskinesias. Thus, this study suggests that diminished buffering capacity for dopamine could play a role in the development of dyskinesias, and that an endogenous mechanism might exist that ameliorates dyskinesias.

Authors+Show Affiliations

The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, CA 94089, USA. dtogasaki@att.netNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15721172

Citation

Togasaki, Daniel M., et al. "Dyskinesias in Normal Squirrel Monkeys Induced By Nomifensine and Levodopa." Neuropharmacology, vol. 48, no. 3, 2005, pp. 398-405.
Togasaki DM, Protell P, Tan LC, et al. Dyskinesias in normal squirrel monkeys induced by nomifensine and levodopa. Neuropharmacology. 2005;48(3):398-405.
Togasaki, D. M., Protell, P., Tan, L. C., Langston, J. W., Di Monte, D. A., & Quik, M. (2005). Dyskinesias in normal squirrel monkeys induced by nomifensine and levodopa. Neuropharmacology, 48(3), 398-405.
Togasaki DM, et al. Dyskinesias in Normal Squirrel Monkeys Induced By Nomifensine and Levodopa. Neuropharmacology. 2005;48(3):398-405. PubMed PMID: 15721172.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dyskinesias in normal squirrel monkeys induced by nomifensine and levodopa. AU - Togasaki,Daniel M, AU - Protell,Peter, AU - Tan,Louis C S, AU - Langston,J William, AU - Di Monte,Donato A, AU - Quik,Maryka, Y1 - 2005/01/28/ PY - 2004/06/08/received PY - 2004/09/27/revised PY - 2004/10/29/accepted PY - 2005/2/22/pubmed PY - 2005/5/25/medline PY - 2005/2/22/entrez SP - 398 EP - 405 JF - Neuropharmacology JO - Neuropharmacology VL - 48 IS - 3 N2 - The mechanisms underlying levodopa-induced dyskinesias are unclear. They might involve impairment of the buffering capacity for dopamine, resulting from loss of nigral dopaminergic cells and the subsequent degeneration of their terminals in striatum. This study investigated the role of striatal buffering in the development of dyskinesias. We used nomifensine, a selective dopamine reuptake blocker, to pharmacologically impair presynaptic buffering capacity in normal squirrel monkeys. Dyskinesias were assessed at 30-min intervals for 4 h after twice-daily treatment with drug. As previously reported by our group, animals receiving levodopa alone (15 mg/kg) exhibited dyskinetic behavior. Treatment with nomifensine alone (3 mg/kg) also induced dyskinesias. Furthermore, combining levodopa with nomifensine significantly increased dyskinesias. Over 4 weeks of treatment, the animals developed tolerance to the dyskinesia-inducing effect of nomifensine. The development of tolerance was prevented by concurrent treatment with levodopa. These results show that impairing buffering by preventing dopamine reuptake can induce dyskinesias and can also augment levodopa-induced dyskinesias. Thus, this study suggests that diminished buffering capacity for dopamine could play a role in the development of dyskinesias, and that an endogenous mechanism might exist that ameliorates dyskinesias. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/15721172/Dyskinesias_in_normal_squirrel_monkeys_induced_by_nomifensine_and_levodopa_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(04)00360-0 DB - PRIME DP - Unbound Medicine ER -