Abstract
A series of racemic and enantiomerically pure oxime derivatives of the potential anti-Parkinson prodrug 6-(N,N-di-n-propylamino)-3,4,5,6,7,8-hexahydro-2H-naphthalen-1-one (1) were synthesized and pharmacologically evaluated. The oximes induced rotational behavior in the Ungerstedt rat rotation model for Parkinson's disease after oral administration. Especially the unsubstituted oxime ((-)-3) and the acetyl-oxime ((-)-10) induced a pronounced and long lasting effect. In this model, large individual differences were observed in responsiveness to treatment between rats. Though less potent than the parent prodrug, the oxime derivatives of (+/-)-1 and (-)-1 can be orally active, acting as cascade prodrugs.
MeSH terms
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Administration, Oral
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Animals
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Antiparkinson Agents / chemical synthesis
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Antiparkinson Agents / chemistry
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Antiparkinson Agents / pharmacology
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CHO Cells
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Cell Line
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Cricetinae
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Disease Models, Animal
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Dopamine Agents / chemical synthesis*
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Dopamine Agents / chemistry
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Dopamine Agents / pharmacology*
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Medial Forebrain Bundle / injuries
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Motor Activity / drug effects
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Motor Activity / physiology
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Naphthalenes / chemical synthesis*
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Naphthalenes / chemistry
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Naphthalenes / pharmacology*
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Neurons / cytology
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Oxidopamine / toxicity
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Oximes / chemical synthesis*
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Oximes / chemistry
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Oximes / pharmacology*
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Parkinson Disease / drug therapy
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Parkinson Disease / metabolism
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacology*
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Rats
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Receptors, Dopamine D1 / genetics
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Receptors, Dopamine D1 / metabolism
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Receptors, Dopamine D2 / genetics
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Receptors, Dopamine D2 / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Stereoisomerism
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Transfection
Substances
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Antiparkinson Agents
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Dopamine Agents
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Naphthalenes
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Oximes
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Prodrugs
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Receptors, Dopamine D1
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Receptors, Dopamine D2
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Recombinant Proteins
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Oxidopamine