Review: A review of the use of zonisamide in Parkinson’s disease

Bermejo, Pedro Emilio; Anciones, B

doi:10.1177/1756285609338501

Cited by 25 publications

(19 citation statements)

References 29 publications

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“…Their deinactivation due to hyperpolarization may amplify membrane oscillations . Ca V 3 Ca 2ϩ channel blockers, such as zonisamide (Bermejo and Anciones 2009;Okada and Kaneko 2011;Tai et al 2011;Yang et al 2014), decrease burst activity of STN neurons and ameliorate PS. Thus, although the effects of DA depletion over SNr neuron firing has been described (Lobb and Jaeger 2015;MacLeod et al 1990;Murer et al 1997;Rohlfs et al 1997;Sanderson et al 1986;Walters et al 2007;Wang et al 2010), not much is known about the ionic mechanisms of pathological firing and whether the different drugs that cause DIP act in the same way.…”

Section: Discussionmentioning

confidence: 99%

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism

Cáceres-Chávez

Hernández-Martínez

Pérez-Ortega

et al. 2018

Journal of Neurophysiology

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Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism. Dopamine (DA) depletion modifies the firing pattern of neurons in the substantia nigra pars reticulata (SNr), shifting their mostly tonic firing toward irregularity and bursting, traits of pathological firing underlying rigidity and postural instability in Parkinson's disease (PD) patients and animal models of Parkinsonism (PS). Drug-induced Parkinsonism (DIP) represents 20 -40% of clinical cases of PS, becoming a problem for differential diagnosis, and is still not well studied with physiological tools. It may co-occur with tardive dyskinesia. Here we use in vitro slice preparations including the SNr to observe drug-induced pathological firing by using drugs that most likely produce it, DA-receptor antagonists (SCH23390 plus sulpiride), to compare with firing patterns found in DA-depleted tissue. The hypothesis is that SNr firing would be similar under both conditions, a prerequisite to the proposal of a similar preparation to test other DIP-producing drugs. Firing was analyzed with three complementary metrics, showing similarities between DA depletion and acute DAreceptor blockade. Moreover, blockade of either nonselective cationic channels or Ca v 3 T-type calcium channels hyperpolarized the membrane and abolished bursting and irregular firing, silencing SNr neurons in both conditions. Therefore, currents generating firing in control conditions are in part responsible for pathological firing. Haloperidol, a DIP-producing drug, reproduced DA-receptor antagonist firing modifications. Since acute DA-receptor blockade induces SNr neuron firing similar to that found in the 6-hydroxydopamine model of PS, output basal ganglia neurons may play a role in generating DIP. Therefore, this study opens the way to test other DIP-producing drugs.NEW & NOTEWORTHY Dopamine (DA) depletion enhances substantia nigra pars reticulata (SNr) neuron bursting and irregular firing, hallmarks of Parkinsonism. Several drugs, including antipsychotics, antidepressants, and calcium channel antagonists, among others, produce drug-induced Parkinsonism. Here we show the first comparison between SNr neuron firing after DA depletion vs. firing found after acute blockade of DA receptors. It was found that firing in both conditions is similar, implying that pathological SNr neuron firing is also a physiological correlate of drug-induced Parkinsonism.

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Section: Discussionmentioning

confidence: 99%

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism

Cáceres-Chávez

Hernández-Martínez

Pérez-Ortega

et al. 2018

Journal of Neurophysiology

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“…This observation offers support for the efficacy of ZNS -a wellknown antiepileptic drug -as a treatment for motor and nonmotor symptoms of PD in a Caucasian man, as already described by Japanese authors. [2][3][4] Moreover, we describe the first use of ZNS in a patient with PD dementia. As previously suggested, [3][4][5][6][7] the main improvements were noted in terms of tremor and bradykinesia.…”

Section: Discussionmentioning

confidence: 99%

Zonisamide for seizures in Parkinson's disease with dementia

Tombini

Pellegrino

Pino

et al. 2013

Seizure

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“…It is also effective P. E. Bermejo in migraine [5], neuropathic pain [6], essential tremor [7], anxiety [8] and other pathologies. ZNS has also been demonstrated to be effective for motor complications of PD and it has an approved clinical indication for treatment of this disease in Japan [9][10][11][12]. However, preliminary evidence proposes that ZNS is effective not only for motor symptoms in PD but may be also useful in the field of ICDs.…”

Section: Introductionmentioning

confidence: 95%

Zonisamide in managing impulse control disorders in Parkinson’s disease

Bermejo

Rodríguez‐Padilla²,

Anciones³

2010

J Neurol

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Impulse control disorders (ICDs) are a set of behaviours that take place in a subgroup of patients with Parkinson's disease (PD). Although reduction or switch of dopamine agonists or decrease of levodopa are the common treatment, this does not always improve the compulsive behaviour. Zonisamide (ZNS) has proved effective for motor symptoms in PD and it may be also useful in the field of ICDs. The aim of our study is to evaluate the safety and efficacy of ZNS in PD patients with ICDs who did not improve following a reduction of either levodopa or dopamine agonists. Fifteen patients were initiated on 25 mg/day ZNS dosage, which was titrated to 200 mg/day, as tolerated. Severity of the behaviours was assessed by means of the Clinical Global Impression and the Barratt Impulsiveness Scale, while motor impairment was assessed by means of the Unified Parkinson's Disease Rating Scale (UPDRS). Demographic data, medication dose, treatment duration and adverse events were also collected and analyzed. There was a marked reduction in the severity of impulsive behaviours and global impulsiveness (mean change from baseline -5.8 to -4.8, respectively). UPDRS changed only marginally. ZNS was generally well tolerated. Our study suggests that ZNS may be effective for ICDs in PD. The lack of studies with other medications to treat these behaviours in PD and the potential beneficial effects of ZNS for motor complications make this drug important in the treatment of the disease.

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Review: A review of the use of zonisamide in Parkinson’s disease

Cited by 25 publications

References 29 publications

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism

Zonisamide for seizures in Parkinson's disease with dementia

Zonisamide in managing impulse control disorders in Parkinson’s disease

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