Modulation of High‐Voltage–Activated Calcium Channels in Dentate Granule Cells by Topiramate

Zhang, Xiao Lei; Velumian, Alexander A.; Jones, Owen; Carlen, Peter L.

doi:10.1111/j.1528-1157.2000.tb02173.x

Cited by 242 publications

(152 citation statements)

References 48 publications

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“…Additional to its ability to antagonize alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors and kainate glutamate receptors [117][118][119], topiramate also facilitates inhibitory GABA A -mediated currents at non-benzodiazepine sites on the GABA A receptor [120,121], inhibits L-type calcium channels and limits calcium-dependent second messenger systems [122], reduces activity-dependent depolarization and excitability of voltage-dependent sodium channels [123], activates potassium conductance [124], and is a weak inhibitor of carbonic anhydrase isoenzymes, CA-II and CA-IV [125], which are found in both neuronal and peripheral tissues. In renal tubules, carbonic anhydrase isoenzyme inhibition reduces hydrogen ion secretion and increases secretion of Na + , K + , , and water, thereby enhancing the likelihood of acidosis and renal stone formation [125,126].…”

Section: Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic Acid Andmentioning

confidence: 99%

Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

Johnson

2008

Biochemical Pharmacology

245

185

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The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence. The Food and Drug Administration (FDA)-approved medications naltrexone and acamprosate have shown mixed results in clinical trials. Oral naltrexone and naltrexone depot formulations have generally demonstrated efficacy at treating alcohol dependence, but their treatment effect size is small, and more research is needed to compare the effects of different doses on drinking outcome. Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. In U.S. trials, acamprosate has not proved to be efficacious. Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate. The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study but not in a multi-site U.S. study. Another FDA-approved medication, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision. Of the non-approved medications, topiramate is among the most promising, with a medium effect size in clinical trials. Another promising medication, baclofen, has shown efficacy in small trials. Serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholic. As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored.

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Section: Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic Acid Andmentioning

confidence: 99%

Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

Johnson

2008

Biochemical Pharmacology

245

185

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“…TOP, which apparently enhances dopaminergic cell death during energy deficiency, inhibits the L type ADCC but stimulates the P/Q, N and R types (36). Conversely, LMT, which appears neuroprotective, inhibits the L, P/Q, N and R types ADCC (37).…”

Section: Discussionmentioning

confidence: 99%

Lamotrigine Is Neuroprotective in the Energy Deficiency Model of MPTP Intoxicated Mice

et al. 2007

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ABSTRACT:The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibits the mitochondrial complex I of the respiratory chain. This results in ATP and ion homeostasis disturbances, which lead to selective death of the substantia nigra dopaminergic neurons. Well known as a Parkinson's disease model, the MPTP animal model also provides a potential paradigm of the energy deficiencies found in childhood. In these conditions, anticonvulsants may provide neuroprotection by limiting cellular energy consumption. We tested valproate, topiramate and lamotrigine in the MPTP mouse model. Dopamine transporter (DAT) density was assessed by quantitative autoradiography, tyrosine hydroxylase (TH) was evaluated by immunohistochemistry and dopamine (DA) levels by HPLC-ED whereas neuronal apoptosis was monitored through active caspase-3. Expectedly, the DAT density, TH immunoreactive neurons and DA content in the MPTP group were respectively reduced to 51%, 40% and 26% versus control animals. Unlike valproate and topiramate, lamotrigine provided a significant neuroprotection against MPTP in maintaining these levels at 99%, 74% and 58% respectively and reducing the induced apoptosis. Altogether, the data indicate that lamotrigine limits dopaminergic neuronal death in the substantia nigra and promotes striatal dendrites sprouting. Lamotrigine, a widely used and well-tolerated molecule in young patients, could represent a valuable adjuvant therapy in various energy deficiency conditions during childhood. (Pediatr Res 62: 14-19, 2007) E vidences from degenerative and metabolic encephalopathies studies indicate that the striatum and the substantia nigra (SN) are vulnerable structures in the brain, especially during pre and postnatal brain development (1,2). A partial or total destruction of this striato-nigral dopaminergic network is found in several conditions occurring in childhood such as iron or copper metabolism abnormalities (1), organic acidurias (3), urea cycle disorders, various mitochondrial energy production deficiencies (1,4), or hypoxia-ischemia (2,5). All these conditions witness the vulnerability of this particular deep nuclei network involved in multiple motor, sensory and cognitive functions.These basal ganglia share a common susceptibility to energetic stress (6,7), which can be studied experimentally using mitochondrial inhibitors (8). Once converted into MPPϩ, the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibits the mitochondrial electron transport chain at complex I (NADH-ubiquinone oxidoreductase) resulting in decreased oxygen consumption and ATP production and ion homeostasis disturbances which, together, lead to neuronal cell death (9). This toxin depletes dopaminergic neurons in the SN and causes neuronal degeneration of the nigrostriatal pathway in animals and humans (9).Several neuroprotection studies were performed in this MPTP mouse model using: energy sparing drugs; free radicals scavengers; anti-glutamatergic drugs; anti-apoptotic molecules and neurotrophines (10 -12).Anticonvulsan...

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“…This activity has been demonstrated mainly at L-type highvoltage-activated calcium channels, in rat dentate gyrus granule cells (Zhang et al 2000). TPM produces a biphasic concentration-response curve, in which a greater reduction in L-type calcium currents was seen at 10 µmol/L than at 50 µmol/L, suggesting a mode of action different from other calcium channel blockers.…”

Section: Antagonism Of Non N-methyl-daspartate Glutamate Receptormentioning

confidence: 97%

Psychopharmacology of topiramate: from epilepsy to bipolar disorder

2006

NDT

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Topiramate (TPM) is one of the novel antiepileptic drugs and exhibits a wide range of mechanisms of action. Efficacy of TPM has been demonstrated in partial-onset seizures and primary generalized seizures in adults and children, as both monotherapy and adjunctive therapy. More recently, TPM has been proposed as an add-on treatment for patients with lithium-resistant bipolar disorder, especially those displaying rapid-cycling and mixed states. This paper reviews the multiple mechanisms of action and the tolerability profile of TPM in the light of its therapeutic potential in affective disorders. Studies of TPM in bipolar disorder are evaluated, and the efficacy and tolerability issues as a mood stabilizing agent are discussed.

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Modulation of High‐Voltage–Activated Calcium Channels in Dentate Granule Cells by Topiramate

Cited by 242 publications

References 48 publications

Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

Lamotrigine Is Neuroprotective in the Energy Deficiency Model of MPTP Intoxicated Mice

Psychopharmacology of topiramate: from epilepsy to bipolar disorder

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