Effects of MK-801, dantrolene, and FK506 on convulsive seizures and brain nitric oxide production in seizure-susceptible EL mice

Nagatomo, Itsugi; Hashiguchi, Wataru; Tominaga, Masataka; Akasaki, Yukio; Uchida, Masahiro; Takigawa, Morikuni

doi:10.1016/s0006-8993(00)03101-2

Cited by 16 publications

(9 citation statements)

References 21 publications

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“…Though dantrolene is most commonly used clinically to treat spasticity, the drug's ability to stabilize abnormal neuronal calcium handling (Chen et al, 2008; Liu et al, 2009; Nagatomo et al, 2001) and to prevent attacks in tottering mice and seizures in other mice (Nagatomo et al, 2001; Swiader et al, 2002) suggests that it could be used similarly to block episodic neuronal dysfunction in patients. Indeed, compounds that regulate calcium signaling, particularly verapamil which is an L-type calcium channel blocker, have been used as treatments for hemiplegic migraine, severe myoclonic epilepsy of infancy and paroxysmal dyskinesia (Hsu et al, 2008; Iannetti et al, 2009; Links et al, 1998; Szczaluba et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Stress, caffeine and ethanol trigger transient neurological dysfunction through shared mechanisms in a mouse calcium channelopathy

Raike

Weisz

Hoebeek

et al. 2013

Neurobiology of Disease

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Several episodic neurological disorders are caused by ion channel gene mutations. In patients, transient neurological dysfunction is often evoked by stress, caffeine and ethanol, but the mechanisms underlying these triggers are unclear because each has diverse and diffuse effects on the CNS. Attacks of motor dysfunction in the CaV2.1 calcium channel mouse mutant tottering are also triggered by stress, caffeine and ethanol. Therefore, we used the tottering mouse attacks to explore the pathomechanisms of the triggers. Despite the diffuse physiological effects of these triggers, ryanodine receptor blockers prevented attacks induced by all of them. In contrast, compounds that potentiate ryanodine receptors triggered attacks suggesting a convergent biochemical pathway. Tottering mouse attacks were both induced and blocked within the cerebellum suggesting that the triggers act locally to instigate attacks. In fact, stress, caffeine and alcohol precipitated attacks in CaV2.1 mutant mice in which genetic pathology was limited to cerebellar Purkinje cells, suggesting that the triggers initiate dysfunction within a specific brain region. The surprising biochemical and anatomical specificity of the triggers and the discovery that the triggers operate through shared mechanisms suggests that it is possible to develop targeted therapies aimed at blocking the induction of episodic neurological dysfunction, rather than treating the symptoms once provoked.

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Section: Discussionmentioning

confidence: 99%

Stress, caffeine and ethanol trigger transient neurological dysfunction through shared mechanisms in a mouse calcium channelopathy

Raike

Weisz

Hoebeek

et al. 2013

Neurobiology of Disease

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show abstract

“…It has been documented that dantrolene suppressed convulsive seizures in EL mice (Nagatomo et al 2001). Dantrolene at very large doses (from 62.5 to 500 mg/kg, i.p.)…”

Section: Effects Of Dantrolene On Seizures In Kindled Ratsmentioning

confidence: 99%

Dantrolene, a Calcium-Induced Calcium Release Inhibitor, Prevents the Acquisition of Amygdaloid Kindling in Rats, a Model of Experimental Epilepsy

Yoshida

Sakai

2006

Tohoku J. Exp. Med.

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Kindling phenomenon (an experimental model of acquired epilepsy) and long-term potentiation (LTP) have many features in common. LTP is associated with an increase in intracellular Ca 2+ concentration where intracellular Ca 2+ stores play an important role. Dantrolene has an inhibitory action against Ca 2+ release from intracellular Ca 2+ stores. This substance has been reported to inhibit the induction of LTP. We investigated whether or not the development of kindling would be inhibited by dantrolene. We first determined at the right amygdala afterdischarge threshold (ADT) that is the minimal electric current necessary to evoke afterdischarge. For investigating the effects of dantrolene on the development of kindling, rats were stimulated once daily at the right amygdala with a current, 10% larger than ADT, one hour after either dantrolene or vehicle had been injected intraperitoneally. We observed daily the progress of both intensities of behavioral seizures (stages of seizures) and the duration of afterdischarge. Dantrolene significantly delayed both the progression of kindling stages and the elongation of afterdischarge duration at a dose of 10 mg/kg or 20 mg/kg, as compared with control vehicle. To investigate the effects of dantrolene on seizures in already kindled rats, we determined generalized seizure threshold (GST) that is the minimum electric current necessary to evoke generalized seizures in fully kindled rats. Rats were stimulated at a current, 10% larger than GST, one hour after treated with the drug or vehicle. Dantrolene showed no anticonvulsant action against either the stages of seizures or afterdischarge durations in fully kindled rats. Therefore, the inhibitory effect of dantrolene on the acquisition of kindling was not attributed to an anticonvulsant action. These results suggest that the prevention of kindling acquisition is associated with an inhibitory action of dantrolene on calcium-induced calcium release from intracellular Ca 2+ stores.

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“…Recent studies have shown that generalized convulsions are an epiphenomenon of NMDA and PKC activation, and NO production (20–22). It is still unknown why these neurochemical processes sometimes result in seizures (first group) and other times do not (second group).…”

Section: Discussionmentioning

confidence: 99%

Severe withdrawal syndrome in three newborns subjected to continuous opioid infusion and seizure activity dependent on brain hypoxia – ischemia. A possible link

Bachiocco¹,

Lorenzini²,

Baroncini³

2006

Pediatric Anesthesia

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Effects of MK-801, dantrolene, and FK506 on convulsive seizures and brain nitric oxide production in seizure-susceptible EL mice

Cited by 16 publications

References 21 publications

Stress, caffeine and ethanol trigger transient neurological dysfunction through shared mechanisms in a mouse calcium channelopathy

Stress, caffeine and ethanol trigger transient neurological dysfunction through shared mechanisms in a mouse calcium channelopathy

Dantrolene, a Calcium-Induced Calcium Release Inhibitor, Prevents the Acquisition of Amygdaloid Kindling in Rats, a Model of Experimental Epilepsy

Severe withdrawal syndrome in three newborns subjected to continuous opioid infusion and seizure activity dependent on brain hypoxia – ischemia. A possible link

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