Action of dopamine agonists on parkinson-like muscle rigidity induced by 6-aminonicotinamide. |
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Authors: | D Loos K Halbhübner W Kehr H Herken |
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Affiliation: | 1. Pharmakologisches Institut der Freien Universität Berlin, Thielallee 69/73. D-1000 Berlin 33, F.R.G.;1. Forschungslaboratorien der Schering AG Berlin/Bergkamen, Müllerstrasse 170-178, D-1000 Berlin 65, F.R.G. |
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Abstract: | In rats, 6-aminonicotinamide and reserpine induce a Parkinson-like persisting or transient muscular rigidity which was registered electromyographically as spontaneous permanent activity in the gastrocnemic muscle. Seven days after application of 6-aminonicotinamide this pathological finding is already fully developed. At the same time a clear decrease in dopamine concentration in the dopamine-rich striatum and a significant slow-down in the utilization of this transmitter is found. The concentration and utilization of noradrenaline in the diencephalon are unchanged.Both on the 6-aminonicotinamide and on the reserpine model, dose response relations for two dopamine agonists (lisuride and α-bromocriptine) were established by means of electromyography. In both models lisuride was fifty times more effective than α-bromocriptine in reducing the elevated electrical activity. In the 6-aminonicotinamide model, however, 10-fold higher doses of both substances were required to reduce the initial pathological effect by half.The dopamine deficit in the striatum and the effects of l-DOPA and dopamine agonists on the 6-aminonicotinamide-induced muscular rigidity imply that the antimetabolite produces a Parkinson-like syndrome. |
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Keywords: | 6-AN 6-aminonicotinamide |
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