Effects of zonisamide on extracellular levels of monoamine and its metabolite, and on Ca2+ ependent dopamine release

Okada, Motohiro; Kaneko, Sunao; Hirano, Takayuki; Ishida, M.; Kondo, Tsuyoshi; Otani, Koichi; Fukushima, Yutaka

doi:10.1016/0920-1211(92)90066-3

Cited by 85 publications

(44 citation statements)

References 18 publications

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“…it decreased striatal dopamine release. However, ZNS at lower than antiepilepticallyrelevant dose of ZNS failed to modulate striatal dopaminergic transmission (Murakami et al, 2001;Okada et al, 1999;Okada et al, 1992;Okada et al, 1995;Yamamura et al, 2009b). These results suggest possible differences in the mechanisms of the antiepileptic and antiparkinsonian actions of ZNS.…”

Section: Antiparkinsonian Mechanisms Of Znsmentioning

confidence: 45%

“…At therapeutically-relevant dose, ZNS increases extracellular levels of monoamines, whereas ZNS at supra-therapeutic dose decreases monoamine release Murakami et al, 2001;Okada et al, 1999;Okada et al, 1992;Okada et al, 1995;Okada et al, 2002). Similar to its effect on the release of monoamines, both acute and chronic administration of therapeutically-relevant doses of ZNS enhance the turnover of dopamine and serotonin (i.e., monoamine synthesis) Okada et al, 1992;Okada et al, 1995). In addition, ZNS inhibits monoamine oxidase activity.…”

Section: Effects Of Zns On Monoamine Releasementioning

confidence: 94%

“…In addition, ZNS inhibits monoamine oxidase activity. These stimulatory effects of ZNS on monoaminergic transmission, via enhancement of monoamine synthesis and release with inhibition of monoamine degradation, are observed after chronic administration Okada et al, 1992;Okada et al, 1995).…”

Section: Effects Of Zns On Monoamine Releasementioning

confidence: 99%

“…Systemic administration of ZNS affects monoamine release in the hippocampus, frontal cortex and striatum in a biphasic dose-dependent manner Murakami et al, 2001;Okada et al, 1999;Okada et al, 1992;Okada et al, 1995;Okada et al, 2002). At therapeutically-relevant dose, ZNS increases extracellular levels of monoamines, whereas ZNS at supra-therapeutic dose decreases monoamine release Murakami et al, 2001;Okada et al, 1999;Okada et al, 1992;Okada et al, 1995;Okada et al, 2002).…”

Section: Effects Of Zns On Monoamine Releasementioning

confidence: 99%

“…However, subsequent pharmacological studies have demonstrated that the target molecules of ZNS include T-type voltage-sensitive Ca 2+ channel (Kito et al, 1996;Suzuki et al, 1992), Ca 2+ induced Ca 2+ releasing system (CICR) (Yamamura et al, 2009b;Yoshida et al, 2005), carbonic anhydrase (Yamamura et al, 2009a), redox (Tokumaru et al, 2000;Ueda et al, 2005;Ueda et al, 2003), neuronal depolarization-induced glutamate release (Okada et al, 1998;, enhancement of release of inhibitory neurotransmitters, e.g., GABA , dopamine and serotonin (Murakami et al, 2001;Okada et al, 1999;Okada et al, 1992;Okada et al, 1995) and lack of affinity to GABA A receptor (Rock et al, 1989). With regard to its antiparkinsonian action, ZNS enhances both the turnover and release of dopamine, and inhibits MAO-B activity and dopaminergic oxidative stress (Asanuma et al, 2008;Komatsu et al, 2000;Leppik, 2004;Mori et al, 1998;Murata, 2004;Okada et al, 1992;Okada et al, 1995;Ueda et al, 2005). While the typical dose of ZNS is 300 to 600 mg/day for patients with epilepsy (Seino et al, 1988), a significant improvement in motor symptoms is reported in patients of Parkinson's disease treated with only 25 to 100 mg/day of ZNS (Murata, 2004;Murata et al, 2007).…”

Section: Antiepileptic Mechanisms Of Znsmentioning

confidence: 99%

See 4 more Smart Citations

Different Mechanisms Underlying the Antiepileptic and Antiparkinsonian Effects of Zonisamide

Okada¹,

Kaneko²

2011

Novel Treatment of Epilepsy

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Section: Antiparkinsonian Mechanisms Of Znsmentioning

confidence: 45%

Section: Effects Of Zns On Monoamine Releasementioning

confidence: 94%

Section: Effects Of Zns On Monoamine Releasementioning

confidence: 99%

Section: Effects Of Zns On Monoamine Releasementioning

confidence: 99%

Section: Antiepileptic Mechanisms Of Znsmentioning

confidence: 99%

See 3 more Smart Citations

Different Mechanisms Underlying the Antiepileptic and Antiparkinsonian Effects of Zonisamide

Okada¹,

Kaneko²

2011

Novel Treatment of Epilepsy

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Zonisamide for Weight Loss in Obese Adults

Gadde

Franciscy²,

Wagner³

et al. 2003

JAMA

258

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HE PREVALENCE OF OBESITY HAS increased dramatically in the past decade in the United States and many other developed countries. 1,2 Because obesity is associated with a significantly increased risk for type 2 diabetes, coronary heart disease, hypertension, numerous other major illnesses, and overall mortality from all causes, 3,4 weight reduction is critical for the obese patient. 5,6 There is good evidence that pharmacotherapy can enhance weight loss when combined with interventions aimed at changing lifestyle, 7 although pharmacological therapies currently approved by the US Food and Drug Administration fail to provide adequate benefit for many obese patients because of adverse effects, contraindications, or lack of positive response. 7 Hence, there is impetus for developing new treatments for the management of obesity. Zonisamide is a marketed antiepileptic drug. In short-term clinical trials of zonisamide in epileptic patients concomitantly receiving other antiepileptic agents, weight loss was an adverse effect. 8 Whereas the anticonvulsant activity of zonisamide is believed to be related to its sodium and calcium channel (T-type) blocking activity, 8 this drug is also known to exert dose-dependent biphasic dopaminergic 9 and serotonergic 10 activity. With this backg r o u n d , w e h y p o t h e s i z e d t h a t zonisamide would be therapeutic for obese patients seeking to lose weight. METHODS This study was conducted at Duke University Medical Center, Durham, NC, from March 2001 to March 2002. The protocol was approved by the medical center's institutional review board before the trial began. Study Participants Study participants were selected from the clinic patient population and those responding to advertisement fliers posted in the local area, and were enrolled between March 2001 and July 2001. Sixty-eight individuals were screened for participation and 60 were

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The role of dopamine in epilepsy

Starr

1996

Synapse

241

157

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The clinical benefits of dopamine agonists in the management of epilepsy can be traced back over a century, whilst the introduction of neuroleptics into psychiatry practice 40 years ago witnessed the emergence of fits as a side effect of dopamine receptor blockade. Epidemiologists noticed a reciprocal relationship between the supposed dopaminergic overactivity syndrome of schizophrenia and epilepsy, which came to be regarded as a dopamine underactivity condition. Early pharmacological studies of epilepsy employed nonselective drugs, that often did not permit dopamine's antiepileptic action to be clearly dissociated from that of other monoamines. Likewise, the biochemical search for genetic abnormalities in brain dopamine function, as predeterminants of spontaneous epilepsy, proved largely inconclusive. The discovery of multiple dopamine receptor families (D1 and D2), mediating opposing influences on neuronal excitability, heralded a new era of dopamine‐epilepsy research. The traditional anticonvulsant action of dopamine was attributed to D2 receptor stimulation in the forebrain, while the advent of selective D1 agonists with proconvulsant properties revealed for the first time that dopamine could also lower the seizure threshold from the midbrain. Whilst there is no immediate prospect of developing D2 agonists or D1 antagonists as clinically useful antiepileptics, there is a growing awareness that seizures might be precipitated as a consequence of treating other neurological disorders with D2 antagonists (schizophrenia) or D1 agonists (parkinsonism). © 1996 Wiley‐Liss, Inc.

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Effects of zonisamide on extracellular levels of monoamine and its metabolite, and on Ca2+ ependent dopamine release

Cited by 85 publications

References 18 publications

Different Mechanisms Underlying the Antiepileptic and Antiparkinsonian Effects of Zonisamide

Different Mechanisms Underlying the Antiepileptic and Antiparkinsonian Effects of Zonisamide

Zonisamide for Weight Loss in Obese Adults

The role of dopamine in epilepsy

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