Rational Drug Use Analysis of Parkinson's Disease with the First Time Attack of Epilepsy / 中国药师

Objective:To bring to doctors' attention to the first time attack of epilepsy in the patients with Parkinson' s disease, enhance the rational drug use and reduce the occurrence of adverse reactions in clinics. Methods: A Parkinson patient with the first time attack of epilepsy was synthetically analyzed on the mechanism of disease, therapy regimen and pharmaceutical care. Results:It was difficult to distinguish the symptom of epilepsy during the treatment of Parkinson' s disease from that of L-dopa induced dyskinesia, therefore, the suitable treatment was difficult to perform. Moreover, antiepileptic drug valproic acid could aggravate Parkinson syn-drome imperceptibly, which was easy to be ignored in clinics. Conclusion:L-dopa induced dyskinesia should try to avoid during the treatment of Parkinson, and should distinguish from the first time attack of epilepsy in order to choose proper antiepileptic drugs.

Palmitoyl Serotonin Inhibits L-dopa-induced Abnormal Involuntary Movements in the Mouse Parkinson Model

L-3,4-dihydroxyphenylalanine (L-DOPA) is the most common treatment for patients with Parkinson's disease (PD). However, long term use of L-DOPA for PD therapy lead to abnormal involuntary movements (AIMs) known as dyskinesia. Fatty acid amide hydrolase (FAAH) is enriched protein in basal ganglia, and inhibition of the protein reduces dyskinetic behavior of mice. Palmitoyl serotonin (PA-5HT) is a hybrid molecule patterned after arachidonoyl serotonin, antagonist of FAAH. However, the effect of PA-5HT on L-DOPA-induced dyskinesia (LID) in PD have not yet been elucidated. To investigate whether PA-5HT relieve LID in PD and decrease hyperactivation of dopamine D1 receptors, we used the 6-hydroxydopomine (6-OHDA)-lesioned mouse model of PD and treated the L-DOPA (20 mg/kg) for 10 days with PA-5HT (0.3 mg/kg/day). The number of wall contacts with the forelimb in the cylinder test was significantly decreased by 6-OHDA lesion in mice and the pharmacotherapeutic effect of L-DOPA was also revealed in PA-5HT-treated mice. Moreover, in AIMs test, PA-5HT-treated mice showed significant reduction of locomotive, axial, limb, and orofacial AIMs score compared to the vehicle-treated mice. LID-induced hyper-phosphorylation of ERK1/2 and overexpression of FosB/ΔFosB was markedly decreased in 6-OHDA-lesioned striatum of PA-5HT-treated mice, indicating that PA-5HT decreased the dopamine D1 receptor-hyperactivation induced by chronic treatment of L-DOPA in dopamine-denervated striatum. These results suggest that PA-5HT effectively attenuates the development of LID and enhance of ERK1/2 phosphorylation and FosB/ΔFosB expression in the hemi-parkinsonian mouse model. PA-5HT may have beneficial effect on the LID in PD.