Effects of classical and novel agents in a MPTP-induced reversible model of Parkinson's disease.
A modified primate model of Parkinson's disease was developed to assess the effectiveness of various agents that act via dopamine, acetylcholine, serotonin or glutamate systems. Using a MPTP dosing regimen a reversible parkinsonian-like syndrome was produced in the marmoset. An obvious advantage of such a protocol is that it allows multiple drug studies to be undertaken in animals, without the need for prolonged anti-parkinsonian therapy to maintain their health. Results show that dopamine D2 agonists (bromocriptine, quinpirole, N,N-dipropyl,A,5,6-DTN, (+)3PPP and PHNO), anti-muscarinics (atropine, scopolamine and benztropine), in addition to L-DOPA and nomifensine, all reduced the bradykinesia induced by MPTP. The D1 agonist SKF-38393 and the partial dopamine agonist (-)3PPP were both ineffective. Finally, agents with potential therapeutic use in Parkinson's disease were also tested. However, a glutamate antagonist (MK801) and three serotonin antagonists (ritanserin, ketanserin and ICI 170,809) were all unable to alter the MPTP effects, at the doses used in our study.
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S P
SP
Department of Neuropharmacology, Glaxo Group Research Ltd., Ware, Hertfordshire, UK.
Elliott
P J
PJ
Hayes
A G
AG
Marriott
A S
AS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002143:Callitrichinae; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D010277:Parasympathomimetics / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D010277:Parasympathomimetics; D017981:Receptors, Neurotransmitter; D012702:Serotonin Antagonists; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine