Effects of zonisamide on dopaminergic system

Okada, Motohiro; Kaneko, Sunao; Hirano, Takayuki; Mizuno, Kazuhisa; Kondo, Tuyoshi; Otani, Koichi; Fukushima, Yutaka

doi:10.1016/0920-1211(95)00078-x

Cited by 170 publications

(100 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Antiepileptics have also been shown to potentiate both typical and atypical antipsychotic-induced prefrontal cortical dopamine release in the rat (Ichikawa et al, 2005) by 5-HT 1A receptor activation (Ichikawa and Meltzer, 1999). D 2 receptor agonists are known to inhibit feeding in rats (Kuo, 2002;Terry et al, 1995); therefore, it is also possible that the anorectic properties of ZNS may relate to the augmentation of dopamine synthesis and/or stimulation of D 2 receptors (Okada et al, 1995). The antiepileptic activity of ZNS may be mediated by a decreased production of GABA transporters, resulting in increased tissue and synaptic concentrations of GABA and enhanced GABA mediated neuronal inhibition (Czapinski et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

Wallingford

Sinnayah

Bymaster

et al. 2008

Neuropsychopharmacol

View full text Add to dashboard Cite

Olanzapine (OLZ), one of the second-generation atypical antipsychotics (SGAs), has shown relative advantages in patient adherence and outcomes. However, OLZ has also been associated with a higher incidence of weight gain than most other SGAs. Excessive weight gain may in turn contribute to long-term health concerns for some individuals. Zonisamide (ZNS), a medication approved in the United States as an adjunct in the management of epilepsy, has a diverse pharmacological profile, including sodium channel blockade, monoamine enhancement, and inhibition of carbonic anhydrase. ZNS has also been reported to cause weight loss in both humans and rodents. We hypothesized that this profile might be beneficial when co-administered with OLZ. To test this hypothesis, we evaluated the effects of OLZ on body weight, as well as the pathways known to regulate feeding behavior and arousal in the Sprague-Dawley rat. As indicated via c-Fos expression, we found an OLZ-induced activation in the nucleus accumbens and orexin neurons in the lateral hypothalamus. An OLZ-associated development of hyperphagia, weight gain and elevated blood glucose in the rat was also found. These outcomes were attenuated and reversed in the presence of concomitant ZNS. These results suggest the hypothesis that ZNS may effectively treat or prevent weight gain or metabolic changes associated with the SGAs. Future studies of this combination in patients through appropriately designed human clinical studies are encouraged.

show abstract

Section: Discussionmentioning

confidence: 99%

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

Wallingford

Sinnayah

Bymaster

et al. 2008

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…ZNS, an antiepileptic drug developed in Japan (13,14), has several mechanisms of action, including inactivation of voltage-sensitive Na+ channels and T-type calcium channels (1 5,16). The drug also appears to modulate the dopaminergic system (17) and to accelerate the release of (y)aminobutyric acid (GABA) from hippocampal slices obtained from the El mouse (1 8). Prior work using electron spin resonance spectroscopy (1 2) showed that ZNS has the free radical scavenging activity of 1,l -diphenyl-2-picrylhydrazyl radicals.…”

Section: Discussionmentioning

confidence: 99%

Zonisamide Reduces the Increase in 8‐Hydroxy‐2′‐Deoxyguanosine Levels Formed During Iron‐Induced Epileptogenesis in the Brains of Rats

2000

View full text Add to dashboard Cite

Summary:Purpose: To examine the change of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, which are used as a marker for oxidative DNA damage, in iron-induced epileptogenic foci of the rat cerebrum. Method: Male Wistar rats were given a cortical injection of ferric chloride, and their 8-OHdG levels were determined over time. Additional animals were pretreated with the antiepileptic drug zonisamide (ZNS) before the ferric chloride injection, and their 8-OHdG levels were compared with the nonpretreated rats. Results: Fifteen minutes after ferric chloride solution injection, the level of 8-OHdG increased, reaching a maximum 30 minutes after injection. Sixty minutes after injection, the levels coincided with those of controls. ZNS. in concentrations of 50 and 100 mg/kg body weight, prevented the increase of 8-OHdG levels within the cerebrum 30 minutes after iron solution injection. Conclusions:These results indicate that the formation of ironinduced epileptogenic foci in rats is related to DNA-damageinduced reactive oxygen species and that the inhibition of 8-OHdG formation by ZNS after iron injection may be due to the drug's antioxidant activity. The data suggest that free radical species known to be formed during iron salts-induced focal epileptogenesis cause damage to isocortical DNA. Furthermore, ZNS appears to inhibit the focal injuring response to DNA that occurs following iron salts-induced acute epileptogenesis.

show abstract

“…Studies suggest that zonisamide may increase dopamine transmission by activating tyrosine hydroxylase (TH) and inhibiting MAO-B activity [7]. In a study conducted in rats, zonisamide increased intra-and extracellular levels of dopamine in the striatum [8]. In addition, nondopaminergic effects of zonisamide have also been reported recently.…”

Section: Discussionmentioning

confidence: 89%

Improvement in Parkinsonism with Zonisamide Treatment in a Patient with Dementia with Lewy Bodies

Taguchi

Takashima²,

Tanaka³

2014

JNSK

View full text Add to dashboard Cite

Effects of zonisamide on dopaminergic system

Cited by 170 publications

References 34 publications

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

Zonisamide Reduces the Increase in 8‐Hydroxy‐2′‐Deoxyguanosine Levels Formed During Iron‐Induced Epileptogenesis in the Brains of Rats

Improvement in Parkinsonism with Zonisamide Treatment in a Patient with Dementia with Lewy Bodies

Contact Info

Product

Resources

About