The effects of gabapentin on different ligand- and voltage-gated currents in isolated cortical neurons.
A clear picture of the mechanisms of action of the anti-epileptic agent gabapentin is far from being accomplished. We have analyzed the effects of gabapentin on ligand- and voltage-gated currents in isolated adult rat cortical neurons. Gabapentin failed to modify glutamate currents and produced a slight reduction of GABA responses. Negligible inhibition of sodium, but consistent inhibition of high-voltage-activated calcium conductance was promoted by gabapentin. In addition, gabapentin reduced calcium current sensitivity to dihydropyridine agonist and antagonists. Interestingly, gabapentin also decreased a not-inactivating, cadmium-sensitive, potassium current. These unconventional effects might underlie its efficacy in a variety of diseases which involve periodic discharge patterns as neuropathic pain or essential tremor.
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale Santa Lucia, Via Ardeatina 306, 00179, Rome, Italy. stefani@uniroma2.it
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Stefani
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Spadoni
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Giacomini
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Lavaroni
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Bernardi
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D003509:Cyclohexanecarboxylic Acids; D000077206:Gabapentin; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D002120:Calcium Channel Agonists; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D015221:Potassium Channels; D015222:Sodium Channels; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester