Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P80404 (GABA transaminase)
 786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Established antiepileptic drugs (AEDs) decrease membrane excitability by interacting with neurotransmitter receptors or ion channels. AEDs developed before 1980 appear to act on sodium channels, gamma-aminobutyric acid type A (GABAA) receptors, or calcium channels. Benzodiazepines and barbiturates enhance GABAA receptor-mediated inhibition. Phenytoin (PHT), carbamazepine (CBZ), and possibly valproate (VPA) decrease high-frequency repetitive firing of action potentials by enhancing sodium-channel inactivation. Ethosuximide (ESM) and VPA reduce a low threshold (T-type) calcium-channel current. The mechanisms of action of the new AEDs are not fully established. Gabapentin (GBP) binds to a high-affinity site on neuronal membranes in a restricted regional distribution of the central nervous system. This binding site may be related to a possible active transport process of GBP into neurons; however, this has not been proven, and the mechanism of action of GBP remains uncertain. Lamotrigine (LTG) decreases sustained high-frequency repetitive firing of voltage-dependent sodium action potentials that may result in a preferential decreased release of presynaptic glutamate. The mechanism of action of oxcarbazepine (OCBZ) is not known; however, its similarity in structure and clinical efficacy to CBZ suggests that its mechanism of action may involve inhibition of sustained high-frequency repetitive firing of voltage-dependent sodium action potentials. Vigabatrin (VGB) irreversibly inhibits GABA transaminase, the enzyme that degrades GABA, thereby producing greater available pools of presynaptic GABA for release in central synapses. Increased activity of GABA at postsynaptic receptors may underline the clinical efficacy of VGB.
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PMID:Antiepileptic drug mechanisms of action. 878 10

Established antiepileptic drugs (AEDs) decrease membrane excitability by interacting with neurotransmitter receptors or ion channels. AEDs developed prior to 1980 appear to act on sodium channels. gamma-amino butyric acid type A (GABAA) receptors (GABARs) or calcium channels. Benzodiazepines and barbiturates enhance GABAR-mediated inhibition. Phenytion, carbamazepine and possibly sodium valproate decrease high-frequency repetitive firing of action potentials by enhancing sodium channel inactivation. Ethosuximide and sodium valproate reduce a low threshold (T-type) calcium channel current. The mechanisms of action of the new AEDs are not fully established. Gabapentin binds to a high affinity site on neuronal membranes in a restricted regional distribution of the central nervous system. This binding site may be related to a possible active transport process of gabapentin into neurons; however, this has not been proven and the mechanism of action of gabapentin remains uncertain. Lamotrigine decreases sustained high-frequency repetitive firing of voltage-dependent sodium actin potentials that may result in a preferential decreased release of presynaptic glutamate. Oxcarbazepine's mechanism of action is not known; however, its similarity in structure and clinical efficacy to that of carbamazepine suggests that its mechanism of action may involve inhibition of sustained high-frequency repetitive firing of voltage-dependent sodium action potentials. Vigabatrin irreversibly inhibits GABA transaminase, the enzyme that degrades GABA, thereby producing greater available pools of presynaptic GABA for release in central synapses. Increased activity of GABA at postsynaptic receptors may underlie the clinical efficacy of vigabatrin. The potential mechanistic bases for rational polypharmacy are reviewed.
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PMID:Is there a mechanistic basis for rational polypharmacy? 929 30