Preliminary study of zonisamide monotherapy in <i>de novo</i> patients with early Parkinson's disease

Ikeda, Ken; Hanashiro, Sayori; Sawada, Masahiro; Iwasaki, Yasuo

doi:10.1111/ncn3.179

Cited by 7 publications

(6 citation statements)

References 23 publications

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“…In 2009, ZNS was approved as an anti-PD drug that was an adjunctive therapy for PD in Japan. ZNS monotherapy ameliorated motor and sleep dysfunction in de novo patients with early-stage PD [14]. Previous experimental studies also revealed that ZNS attenuated loss of dopaminergic neurons in animal models of PD [15][16][17][18].…”

Section: Introductionmentioning

confidence: 82%

Zonisamide cotreatment delays striatal dopamine transporter reduction in Parkinson disease: A retrospective, observational cohort study

Ikeda

Yanagihashi

Muramatsu

et al. 2018

Journal of the Neurological Sciences

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This study examined whether zonisamide (ZNS) cotreatment delays dopamine transporter (DAT) reduction on SPECT in Parkinson disease (PD) patients. The study participants met the following criteria: (i) age ≥ 40 years; (ii) HY stage = 2 or 3; (iii) average specific binding ratio (SBR) ≥2.00; (iv) levodopa administration without a prior history of ZNS use before the first DAT-SPECT (baseline). Attending physicians initially determined whether ZNS (25 mg/day) should be used or not. Levodopa and other anti-PD medications were not restricted. The second DAT-SPECT (endpoint) was conducted 1.2 ± 0.2 years after the first DAT-SPECT. Clinicoradiological changes of HY stage, UPDRS parts II to IV, dyskinesia subscore, and SBR were calculated. Statistical differences were analyzed by Student's t-test, ANOVA, or multilogistic analysis. ZNS cotreatment improved wearing off and prevented the development of dyskinesia without additional administration of selegiline, entacapone, and dopamine receptor agonists. The endpoint SBR reduced significantly in the non-ZNS group compared to the baseline (P < .01). The SBR decline rate reduced significantly in the ZNS group (P < .01). ZNS was an independent preventive factor for SBR reduction. These results suggested a beneficial potential that ZNS preserves striatal presynaptic DAT expression and slows disease progression in early-stage PD.

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Section: Introductionmentioning

confidence: 82%

Zonisamide cotreatment delays striatal dopamine transporter reduction in Parkinson disease: A retrospective, observational cohort study

Ikeda

Yanagihashi

Muramatsu

et al. 2018

Journal of the Neurological Sciences

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“…Now, zonisamide is approved as an adjunctive treatment in patients with advanced PD who show insufficient response to levodopa treatment. Moreover, recently, it has been reported that zonisamide monotherapy is effective for treatment in de novo patients with early PD [8].…”

Section: Introductionmentioning

confidence: 99%

Zonisamide Enhances Motor Effects of Levodopa, Not of Apomorphine, in a Rat Model of Parkinson’s Disease

Nishijima

Miki

Ueno

et al. 2018

Parkinson's Disease

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Zonisamide is a relatively recent drug for Parkinson's disease. Multiple hypotheses have been proposed to explain the antiparkinsonian effects of zonisamide. However, it is still unclear whether the effect of zonisamide is mainly due to dopaminergic modification in the striatum, or if zonisamide works through nondopaminergic pathways. We conducted the present study to determine the mechanism that is mainly responsible for zonisamide's effects in Parkinson's disease. We examined the effects of zonisamide on motor symptoms in a hemiparkinsonian rat model when administered singly, coadministered with levodopa, a dopamine precursor, or apomorphine, a D1 and D2 dopamine receptor agonist. We used 6-hydroxydopamine-lesioned hemiparkinsonian rats, which were allocated to one of five groups: 14 rats received levodopa only (6 mg/kg), 12 rats received levodopa (6 mg/kg) plus zonisamide (50 mg/kg), six rats received apomorphine only (0.05 mg/kg), six rats received apomorphine (0.05 mg/kg) plus zonisamide (50 mg/kg), and six rats received zonisamide only (50 mg/kg). The drugs were administered once daily for 15 days. We evaluated abnormal involuntary movement every 20 min during a 3 h period following the injection of drugs on treatment Days 1, 8, and 15. Western blot analyses for dopamine decarboxylase and vesicular monoamine transferase-2 were performed using striatal tissues in the lesioned side of rats in the levodopa only group (n = 6) and levodopa plus zonisamide group (n = 4). Levodopa-induced abnormal involuntary movement was significantly enhanced by coadministration of zonisamide. In contrast, zonisamide had no effect on apomorphine-induced abnormal involuntary movement. Zonisamide monotherapy did not induce abnormal involuntary movement. Zonisamide did not affect striatal expression of dopamine decarboxylase or vesicular monoamine transferase-2. In conclusion, zonisamide appears to generate its antiparkinsonian effects by modulating levodopa-dopamine metabolism in the parkinsonian striatum.

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“…ZNS, 1,2-benzisoxazole-3-methanesulfonamide, has been used for more than 20 years as an anti-epileptic drug in Japan (35). This medication was reported to ameliorate motor symptoms on UPDRS part III in PD patients (36-38). In 2009, ZNS was approved as an adjunctive therapy for Japanese PD patients.…”

Section: Dat Binding Modulation After Anti-pd Medicationsmentioning

confidence: 99%

Dopamine Transporter Imaging in Parkinson Disease: Progressive Changes and Therapeutic Modification after Anti-parkinsonian Medications

et al. 2019

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Parkinson disease (PD) is a slowly progressive neurodegenerative disease characterized by the loss of dopaminergic neurons and terminals in the nigrostriatal system. Dopamine transporter (DAT) imaging is widely performed for the differential diagnosis of PD and other degenerative parkinsonism from essential tremor, vascular parkinsonism, and drug-induced parkinsonism. DAT is the plasma membrane carrier specific to dopamine neurons that are responsible for re-uptaking dopamine from the synaptic cleft back into the nerve ending. DAT binding might reflect striatal presynaptic dysfunction or DAT expression in PD patients. Longitudinal studies of DAT imaging have reported progressive changes from early PD patients. This imaging may be used as a progressive biomarker. Follow-up DAT imaging for therapeutic interventions has been applied for several anti-parkinsonian drugs. We herein review the progressive changes and therapeutic modification of DAT binding by anti-PD medications in early PD patients.

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Preliminary study of zonisamide monotherapy in de novo patients with early Parkinson's disease

Cited by 7 publications

References 23 publications

Zonisamide cotreatment delays striatal dopamine transporter reduction in Parkinson disease: A retrospective, observational cohort study

Zonisamide cotreatment delays striatal dopamine transporter reduction in Parkinson disease: A retrospective, observational cohort study

Zonisamide Enhances Motor Effects of Levodopa, Not of Apomorphine, in a Rat Model of Parkinson’s Disease

Dopamine Transporter Imaging in Parkinson Disease: Progressive Changes and Therapeutic Modification after Anti-parkinsonian Medications

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