Abstract
After decades of research around dopamine agonists, we have found a promising compound in S-PD148903 that represents a new type of prodrug, which in the rat is bioactivated to the catecholamine S-5,6-diOH-DPAT, known to display mixed dopamine D(1)/D(2) receptor agonist properties just like apomorphine. This prodrug has an enone structure which by an oxidative bioactivation mechanism is converted to the corresponding catechol and is delivered enantioselectively into the CNS. This novel concept has the potential to revolutionize the treatment of Parkinson's disease by competing with L-DOPA, the current treatment of choice.
MeSH terms
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2-Naphthylamine / analogs & derivatives
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2-Naphthylamine / chemical synthesis*
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2-Naphthylamine / metabolism
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2-Naphthylamine / pharmacology
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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 / metabolism
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Antiparkinson Agents / pharmacology
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Catecholamines / chemical synthesis*
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Catecholamines / metabolism
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Catecholamines / pharmacology
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Crystallography, X-Ray
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Male
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Microdialysis
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Molecular Conformation
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Parkinson Disease / drug therapy*
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Parkinson Disease / physiopathology
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Prodrugs / chemical synthesis*
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Prodrugs / metabolism
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Prodrugs / pharmacology
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Rats
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Rats, Wistar
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Receptors, Dopamine D1 / agonists
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Receptors, Dopamine D2 / agonists
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Stereoisomerism
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Structure-Activity Relationship
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Tetrahydronaphthalenes / administration & dosage
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Tetrahydronaphthalenes / metabolism*
Substances
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Antiparkinson Agents
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Catecholamines
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PD 148903
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Prodrugs
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Receptors, Dopamine D1
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Receptors, Dopamine D2
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Tetrahydronaphthalenes
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2-(N,N-dipropyl)amino-5,6-dihydroxytetralin
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2-Naphthylamine