Biphasic effects of zonisamide on serotonergic system in rat hippocampus

Okada, Motohiro; Hirano, Takayuki; Kawata, Y.; Murakami, Takuya; Wada, Kazumaru; Mizuno, Kazuhisa; Kondo, Tuyoshi; Kaneko, Sunao

doi:10.1016/s0920-1211(98)00109-0

Cited by 81 publications

(40 citation statements)

References 35 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: 86%

“…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).…”

Section: Antiepileptic Mechanisms Of Znsmentioning

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%

“…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).…”

Section: Effects Of Zns On Monoamine Releasementioning

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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Section: Antiparkinsonian Mechanisms Of Znsmentioning

confidence: 86%

Section: Antiepileptic Mechanisms Of Znsmentioning

confidence: 99%

Section: Effects Of Zns On Monoamine Releasementioning

confidence: 99%

Section: Effects Of Zns On Monoamine Releasementioning

confidence: 99%

See 2 more Smart Citations

Different Mechanisms Underlying the Antiepileptic and Antiparkinsonian Effects of Zonisamide

Okada¹,

Kaneko²

2011

Novel Treatment of Epilepsy

Self Cite

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“…ZNS modulates GABA-mediated neuronal inhibition [4] and weakly inhibits carbonic anhydrase (CA) activity [5]. ZNS also affects dopaminergic and serotonergic neurotransmission [6]. For more than two decades, ZNS has been used as monotherapy and adjunctive therapy for the treatment of partial and generalized seizures in pediatric and adult patients in Japan [7].…”

Section: Introductionmentioning

confidence: 99%

Moderate toxic effects following acute zonisamide overdose

Hofer¹,

Trachsel

Rauber-Lüthy³

et al. 2011

Epilepsy & Behavior

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Zonisamide is an antiepileptic drug that acts on voltage-sensitive sodium and calcium channels, with a modulatory effect on GABA-mediated neuronal inhibition and an inhibitory effect on carbonic anhydrase. It is used mainly for the treatment of partial seizures, and is generally well tolerated at therapeutic doses. The most common reported adverse effects are somnolence, anorexia, dizziness, and headache. There are limited data on zonisamide overdose in the literature, and no case of zonisamide mono-intoxication has been published to date. We describe the first case of zonisamide mono-intoxication in a 25-year-old woman who ingested 12.6 g of this substance with suicidal intent. Despite a plasma zonisamide concentration of 182 mg/L on admission, the patient exhibited a benign clinical course with vomiting and central nervous system depression, requiring brief intubation. Somnolence persisted for 50 hours, and normal-anion-gap metabolic acidosis and polyuria for several days. Complete recovery may be expected with supportive care, even after ingestion of large zonisamide overdoses.

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Zonisamide for Weight Loss in Obese Adults

Gadde

Franciscy²,

Wagner³

et al. 2003

JAMA

254

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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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Biphasic effects of zonisamide on serotonergic system in rat hippocampus

Cited by 81 publications

References 35 publications

Different Mechanisms Underlying the Antiepileptic and Antiparkinsonian Effects of Zonisamide

Different Mechanisms Underlying the Antiepileptic and Antiparkinsonian Effects of Zonisamide

Moderate toxic effects following acute zonisamide overdose

Zonisamide for Weight Loss in Obese Adults

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