topiramate brands

Molecular formula: C12H21NO8S

A seizure is an abnormal and unregulated electrical discharge occurring in the brain. This leads to transient interruption in brain function, manifested by reduced alertness, abnormal sensations, and focal involuntary movements or convulsions. Several types of seizures exist, with common types including tonic-clonic seizures and partial onset seizures. The exact mechanisms by which topiramate exerts pharmacological actions on seizures and migraines are currently not fully characterized. Several properties of this drug, however, are likely to contribute to its therapeutic effects. Topiramate has been observed to exert actions on voltage-dependent sodium channels, GABA receptors, and glutamate receptors. Topiramate stimulates GABA-A receptor activity at brain non-benzodiazepine receptor sites and reduces glutamate activity at both AMPA and kainate receptors. Normally, GABA-A receptors are inhibitory and glutaminergic receptors are stimulatory for neuronal activity. By increasing GABA activity and inhibiting glutamate activity, topiramate blocks neuronal excitability, preventing seizures and migraines. Additionally, it blocks the voltage-dependent sodium channels, further blocking seizure activity. Topiramate has been shown to inhibit various carbonic anhydrase isozymes, but the clinical significance of this is unknown at this time. The precise mechanism of action is unknown. Electrophysiological and biochemical studies on cultured neurons demonstrated that topiramate blocks the action potentials elicited repetitively by a sustained depolarization of the neurons in a time dependent manner; this effect suggests a state-dependent sodium channel blocking action. Also topiramate increases the frequency at which gamma-aminobutyric acid (GABA) activates GABA-A receptors, thereby enhancing GABA-induced influx of chloride ions into neurons. Thus, it appears that topiramate exerts it effects by potentiation of the activity of the inhibitory neurotransmitter, GABA. In addition, topiramate antagonizes the ability of kainate to activate the kainate/AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid; non-NMDA) subtype of excitatory amino acid (glutamate) receptor, but has no apparent effect on the activity of N-methyl-D-aspartate (NMDA) at the NMDA receptor subtype. These effects of topiramate are concentration-dependent within the range of 1 to 200 micromoles. Although the precise mechanism of action of topiramate is unknown, data from electrophysiologic and biochemical studies have revealed 4 properties that may contribute to the drug's efficacy for seizure disorders and migraine prophylaxis. At pharmacologically relevant concentrations, topiramate blocks voltage-dependent sodium channels; augments the activity of gamma-aminobutyric acid (GABA) at some subtypes of the GABA-A receptor; antagonizes the AMPA/kainate subtype of the glutamate receptor; and inhibits carbonic anhydrase (particularly CA-II and CA-IV isoenzymes). In general, anticonvulsant drugs are thought to act by one or more of the following mechanisms: modulating voltage-dependent ion (e.g., sodium) channels involved in action potential propagation or burst generation, enhancement of GABA inhibitory activity, and/or inhibition of excitatory amino acid neurotransmitter (e.g., glutamate, aspartate) activity. Topiramate exhibits effects on cultured neurons similar to those observed with phenytoin and carbamazepine, and such effects are suggestive of an inactive state-dependent block of voltage-dependent sodium channels. Topiramate reduces the duration of epileptiform bursts of neuronal firing and decreases the number of action potentials in studies of cultured rat hippocampal neurons with spontaneous epileptiform burst activity. Topiramate also decreases the frequency of action potentials elicited by depolarizing electric current in cultured rat hippocampal neurons. Depolarization and firing of an action potential results from the rapid inflow of sodium ions throug

Source: PubChem (NCBI) · compound 5284627