Apomorphine continuous stimulation in Parkinson's disease: receptor desensitization as a possible mechanism of reduced motor response.
Apomorphine is a potent nonselective agonist at D1 and D2 dopamine receptors. The utility of apomorphine in Parkinson's disease (PD) is well asserted but its clinical use is reduced because of its short half-life and numerous side-effects. The disabling "on-off" fluctuations are among the most frequent and troublesome complications of chronic levodopa therapy in PD. Apomorphine is effective to reverse refractory L-dopa induced "off" periods, but a reduced motor response after repeated administrations has also been described with this drug. The loss of response to apomorphine, when the drug is administered repeatedly, is well fitted by the processes of receptor phosphorylation and down regulation. Elucidation of the molecular bases of dopaminergic receptors desensitization may lead to a better understanding of the mechanisms of dopaminergic regulation, and to a more appropriate treatment of PD.
Maggio
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R
Istituto di Farmacologia, Scuola Medica, Università di Pisa, Italy.
Barbier
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P
Corsini
G U
GU
D000978:Antiparkinson Agents / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D001058:Apomorphine / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D009068:Movement / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D013268:Stimulation, Chemical
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D001058:Apomorphine