Gabapentina y pregabalina son estructuralmente similares al neurotrasmisor GABA, aunque estos fármacos no interactúan con el receptor GABA y su efecto terapéutico no se revierte con los antagonistas GABA. Se acepta que ambas drogas interactúan con las subunidades de los canales de calcio α2δ en sus isoformas 1 y 2. El resultado de esta interacción es la reducción de la liberación de neurotrasmisores con un efecto de disminución de la hiperexitabilidad neuronal. Todo esto ocurre de forma presináptica induciendo la baja del influjo de calcio, disminución de glutamato, de sustancia P y de norepinefrina en la sinapsis.
Gabapentin and pregabalin are structurally similar to the neurotransmitter GABA, but these drugs do not interact with the GABA receptor and its therapeutic effect is not reversed by GABA antagonists. It is accepted that both drugs interact with calcium channels in α2δ isoforms 1 and 2. The result of this interaction is to reduce the release of neurotransmitters with an effect of decreasing neuronal hiperexitabilidad. All this occurs lowering presynaptic calcium influx, decreased glutamate, substance P and norepinephrine in synapses.
Gabapentina y pregabalina ligandos A2delta: implicaciones futuras en la clínica diaria
A2delta ligands gabapentin and pregabalin: future implications in daily clinical practice.
Tzellos TG, Papazisis G, Toulis KA, Sardeli Ch, Kouvelas D.
Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Greece.
Hippokratia. 2010 Apr;14(2):71-5.
Abstract
Gabapentin (GP) and pregabalin (PB) are structurally related compounds and their predominant mechanism of action is the inhibition of calcium currents via high-voltage-activated channels containing the a2d-1 subunit. A2delta ligands are approved for the treatment of pain of diabetic neuropathy and post-herpetic neuralgia in adults and as adjunctive therapy of partial seizures in children. Recently, pregabalin has been approved for treatment of anxiety disorders in Europe. Besides their already approved indications both drugs are promising treatment options for a number of different serious and debilitating diseases, as fibromyalgia, neuropathic pain of spinal cord injury, hot flushes, and essential tremor. In the present review, the unique mechanism of action of the above drugs is critically analyzed and evidence for their future use is provided. Gabapentin and pregabalin can be treatment options for these disorders, however, a clear comparison between the two drugs can not be performed, since there is no direct comparison study. The most common side effects are dizziness and somnolence which are also the most frequent reasons for withdrawal. Recommendations for future studies should include assessment of ideal titration period for GP and PB to reduce incidence of somnolence and dizziness and increase tolerability, cost-effectiveness and dose-response analysis of PB and GP and direct comparison of the two drugs.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895293/pdf/hippokratia-14-71.pdf
Mediciones amperométricas de la liberación del glutamato modulada por gabapentina y pregabalina en muestras neocorticales de ratas: papel de la subunidad voltage sensitiva Ca2+ α2δ-1
Amperometric measurement of glutamate release modulation by gabapentin and pregabalin in rat neocortical slices: role of voltage-sensitive Ca2+ α2δ-1 subunit.
Quintero JE, Dooley DJ, Pomerleau F, Huettl P, Gerhardt GA.
Morris K Udall Parkinson's Disease Research Center of Excellence, Center for Microelectrode Technology, Department ofAnatomy and Neurobiology, University of Kentucky, Lexington, Kentucky 40536, USA.george.quintero@uky.edu
J Pharmacol Exp Ther. 2011 Jul;338(1):240-5. Epub 2011 Apr 4.
Abstract
Gabapentin (GBP; Neurontin) and pregabalin (PGB; Lyrica, S-(+)-3-isobutylgaba) are used clinically to treat several disorders associated with excessive or inappropriate excitability, including epilepsy; pain from diabetic neuropathy, postherpetic neuralgia, and fibromyalgia; and generalized anxiety disorder. The molecular basis for these drugs' therapeutic effects are believed to involve the interaction with the auxiliary α(2)δ subunit of voltage-sensitive Ca(2+) channel (VSCC) translating into a modulation of pathological neurotransmitter release. Glutamate as the primary excitatory neurotransmitter in the mammalian central nervous system contributes, under conditions of excessive glutamate release, to neurological and psychiatric disorders. This study used enzyme-based microelectrode arrays to directly measure extracellular glutamate release in rat neocortical slices and determine the modulation of this release by GBP and PGB. Both drugs attenuated K(+)-evoked glutamate release without affecting basal glutamate levels. PGB (0.1-100 μM) exhibited concentration-dependent inhibition of K(+)-evoked glutamate release with an IC(50) value of 5.3 μM. R-(-)-3-Isobutylgaba, the enantiomer of PGB, did not significantly reduce K(+)-evoked glutamate release. The decrease of K(+)-evoked glutamate release by PGB was blocked by the l-amino acid l-isoleucine, a potential endogenous ligand of the α(2)δ subunit. In neocortical slices from transgenic mice having a point mutation (i.e., R217A) of the α(2)δ-1 (subtype) subunit of VSCC, PGB did not affect K(+)-evoked glutamate release yet inhibited this release in wild-type mice. The results show that GBP and PGB attenuated stimulus-evoked glutamate release in rodent neocortical slices and that the α(2)δ-1 subunit of VSCC appears to mediate this effect.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126634/pdf/zpt240.pdf
Atentamente
Anestesiología y Medicina del Dolor
www.anestesia-dolor.org
Gabapentin and pregabalin are structurally similar to the neurotransmitter GABA, but these drugs do not interact with the GABA receptor and its therapeutic effect is not reversed by GABA antagonists. It is accepted that both drugs interact with calcium channels in α2δ isoforms 1 and 2. The result of this interaction is to reduce the release of neurotransmitters with an effect of decreasing neuronal hiperexitabilidad. All this occurs lowering presynaptic calcium influx, decreased glutamate, substance P and norepinephrine in synapses.
Gabapentina y pregabalina ligandos A2delta: implicaciones futuras en la clínica diaria
A2delta ligands gabapentin and pregabalin: future implications in daily clinical practice.
Tzellos TG, Papazisis G, Toulis KA, Sardeli Ch, Kouvelas D.
Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Greece.
Hippokratia. 2010 Apr;14(2):71-5.
Abstract
Gabapentin (GP) and pregabalin (PB) are structurally related compounds and their predominant mechanism of action is the inhibition of calcium currents via high-voltage-activated channels containing the a2d-1 subunit. A2delta ligands are approved for the treatment of pain of diabetic neuropathy and post-herpetic neuralgia in adults and as adjunctive therapy of partial seizures in children. Recently, pregabalin has been approved for treatment of anxiety disorders in Europe. Besides their already approved indications both drugs are promising treatment options for a number of different serious and debilitating diseases, as fibromyalgia, neuropathic pain of spinal cord injury, hot flushes, and essential tremor. In the present review, the unique mechanism of action of the above drugs is critically analyzed and evidence for their future use is provided. Gabapentin and pregabalin can be treatment options for these disorders, however, a clear comparison between the two drugs can not be performed, since there is no direct comparison study. The most common side effects are dizziness and somnolence which are also the most frequent reasons for withdrawal. Recommendations for future studies should include assessment of ideal titration period for GP and PB to reduce incidence of somnolence and dizziness and increase tolerability, cost-effectiveness and dose-response analysis of PB and GP and direct comparison of the two drugs.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895293/pdf/hippokratia-14-71.pdf
Mediciones amperométricas de la liberación del glutamato modulada por gabapentina y pregabalina en muestras neocorticales de ratas: papel de la subunidad voltage sensitiva Ca2+ α2δ-1
Amperometric measurement of glutamate release modulation by gabapentin and pregabalin in rat neocortical slices: role of voltage-sensitive Ca2+ α2δ-1 subunit.
Quintero JE, Dooley DJ, Pomerleau F, Huettl P, Gerhardt GA.
Morris K Udall Parkinson's Disease Research Center of Excellence, Center for Microelectrode Technology, Department ofAnatomy and Neurobiology, University of Kentucky, Lexington, Kentucky 40536, USA.george.quintero@uky.edu
J Pharmacol Exp Ther. 2011 Jul;338(1):240-5. Epub 2011 Apr 4.
Abstract
Gabapentin (GBP; Neurontin) and pregabalin (PGB; Lyrica, S-(+)-3-isobutylgaba) are used clinically to treat several disorders associated with excessive or inappropriate excitability, including epilepsy; pain from diabetic neuropathy, postherpetic neuralgia, and fibromyalgia; and generalized anxiety disorder. The molecular basis for these drugs' therapeutic effects are believed to involve the interaction with the auxiliary α(2)δ subunit of voltage-sensitive Ca(2+) channel (VSCC) translating into a modulation of pathological neurotransmitter release. Glutamate as the primary excitatory neurotransmitter in the mammalian central nervous system contributes, under conditions of excessive glutamate release, to neurological and psychiatric disorders. This study used enzyme-based microelectrode arrays to directly measure extracellular glutamate release in rat neocortical slices and determine the modulation of this release by GBP and PGB. Both drugs attenuated K(+)-evoked glutamate release without affecting basal glutamate levels. PGB (0.1-100 μM) exhibited concentration-dependent inhibition of K(+)-evoked glutamate release with an IC(50) value of 5.3 μM. R-(-)-3-Isobutylgaba, the enantiomer of PGB, did not significantly reduce K(+)-evoked glutamate release. The decrease of K(+)-evoked glutamate release by PGB was blocked by the l-amino acid l-isoleucine, a potential endogenous ligand of the α(2)δ subunit. In neocortical slices from transgenic mice having a point mutation (i.e., R217A) of the α(2)δ-1 (subtype) subunit of VSCC, PGB did not affect K(+)-evoked glutamate release yet inhibited this release in wild-type mice. The results show that GBP and PGB attenuated stimulus-evoked glutamate release in rodent neocortical slices and that the α(2)δ-1 subunit of VSCC appears to mediate this effect.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126634/pdf/zpt240.pdf
Atentamente
Anestesiología y Medicina del Dolor
www.anestesia-dolor.org
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