Novel pharmacological strategies for motor complications in Parkinson's disease
Autor: | Konitsiotis, S. |
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Jazyk: | angličtina |
Rok vydání: | 2005 |
Předmět: |
Antiparkinson Agents/*administration & dosage
Dopamine Agonists/*administration & dosage Enzyme Inhibitors/pharmacology Clinical Trials as Topic Drug Delivery Systems Movement Disorders/drug therapy/metabolism Administration Cutaneous Parkinson Disease/drug therapy/metabolism Signal Transduction/drug effects Liposomes Nitriles Brain/drug effects/metabolism Receptors Glutamate/drug effects/metabolism Animals Humans Indans/pharmacology Drug Therapy Combination Catechol O-Methyltransferase/antagonists & inhibitors/metabolism Catechols/pharmacology Levodopa/*administration & dosage Motor Neurons/*drug effects/enzymology Monoamine Oxidase Inhibitors/pharmacology |
Popis: | In advanced Parkinson's disease, the combination of disease progression and levodopa therapy leads to the development of motor problems complicating the therapeutic response, known as motor response complications. The nonphysiological, pulsatile stimulation produced by most currently available dopaminergic therapies triggers a complicated series of responses resulting in the dysregulation of glutamate receptors and many other neurotransmitter systems on striatal neurons. Although a number of novel compounds that provide a more continuous dopaminergic stimulation are becoming available, no practical way to accomplish this in a truly physiological manner currently exists. Novel strategies for pharmacological intervention with the use of nondopaminergic treatments, with drugs targeting selected transmitter receptors expressed on striatal neurons appear more promising. These include NMDA or AMPA antagonists, or drugs acting on 5-hydroxytryptamine subtype 2A, alpha2-adrenergic, adenosine A2A and cannabinoid CB1 receptors. Future strategies may also target pre- and postsynaptic components that regulate firing pattern, like synaptic vesicle proteins, or nonsynaptic gap junction communication mechanisms, or drugs with actions at the signal transduction systems that modulate the phosphorylation state of NMDA receptors. These new therapeutic strategies, alone or in combination, hold the promise of providing effective control or reversal of motor response complications. Expert Opin Investig Drugs |
Databáze: | OpenAIRE |
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