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

Abstract

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.

An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy

“…In addition to its antiepileptic properties, ZNS has demonstrated neuroprotective properties in experimental models of different conditions of the brain [18,19]. It also acts as an inhibitor of monoamine oxidase B (MAO-B), delays dopamine transporter reduction in Parkinson's disease, and alleviates Parkinsonian motor symptoms [20][21][22]. ZNS has also shown some efficacy as a treatment for migraine and obesity [23,24].…”

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

“…A number of longitudinal DAT imaging studies have described progressive changes in PD patients (8-27). Therapeutic effects of anti-PD medications on DAT binding have also been reported in early PD patients (14, 20, 28-33). The present review highlights the progressive changes and therapeutic modification of DAT binding after the administration of anti-parkinsonian drugs in early PD patients.…”

“…Previous studies described therapeutic effects of several anti-PD drugs on DAT binding in early PD patients (14, 20, 28-33). Changes of DAT binding before and after anti-parkinsonian medication of levodopa, dopamine agonists or zonisamide (ZNS) are summarized in Table 2.…”

Evaluation of Medicinal Effects of Isoxazole Ring Isosteres on Zonisamide for Autism Treatment by Binding to Potassium Voltage-Gated Channel Subfamily D Member 2 (Kv 4.2)

“…Zonisamide later received its FDA approval as an adjuvant treatment for partial seizures in 2000. Over the years, the ameliorative effect of this drug in both partial and generalized seizures [2][3][4][5][6][7] as well as several other neurological disorders namely, psychotic conditions [8], Parkinson disease [9][10][11][12][13], neuropathic pain [14] and essential tremor [15] have been investigated. Although the precise mechanism of Zonisamide has not yet fully understood, blockage of voltagegated sodium channels and T-type calcium channels seems to be the principle route of action.…”