SEARCH · Search PubMed

Results for “Gabapentin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources

PubMed1994

Clinical efficacy and safety of gabapentin.

The challenges of treating patients with partial seizures soon will be met, in part, by a number of new additions (felbamate, gabapentin, lamotrigine) to existing treatment options. Gabapentin, has shown significant promise in the treatment of patients with refractory partial seizures and secondarily generalized tonic-clonic seizures. Three large, randomized, multicenter, double-blind, placebo-controlled, parallel-group clinical trials have established its efficacy and safety as add-on therapy in patients with refractory partial seizures. Gabapentin is well tolerated. Although adverse events occur in most patients receiving gabapentin as adjunctive therapy, they are transient and mild to moderate in severity. To date, serious adverse events have been rare. Long-term safety data are needed. The lack of drug interaction potential between gabapentin and traditional antiepileptic drugs also was confirmed in clinical trials.

Acetates↗

PubMed1993

Effects of gabapentin on release of gamma-aminobutyric acid from slices of rat neostriatum.

The gamma-aminobutyric acid (GABA) analogue gabapentin (CAS 60142-96-3) has a strong anticonvulsant activity in patients, but its mechanism of action is unknown. In the present study, the effect of gabapentin was tested on the release of [3H]GABA from neostriatal slices incubated in vitro. Gabapentin displayed a bell-shaped concentration-response curve. When used at the therapeutically relevant concentration of 1 mumol/l, it nearly doubled the release of [3H]GABA, while it was without effects at concentrations of 0.1 and 10 mumol/l, respectively. The enhancing effect was blocked by the GABAA receptor antagonists picrotoxin (5 mumol/l) and bicucullin (100 mumol/l). When the slices were pre-incubated with the agonist muscimol (1 mumol/l) to occupy the GABAA receptors, 1 mumol/l gabapentin no longer enhanced the release of [3H]GABA. It is concluded that gabapentin can enhance the release of [3H]GABA, when used at a therapeutically relevant concentration. GABAA receptors are involved in this effect which may contribute to the agent's anticonvulsant activity.

Acetates↗

PubMed1995

Gabapentin: pharmacokinetics, efficacy, and safety.

Gabapentin is a new antiepileptic drug (AED) with an attractive pharmacokinetic profile. It is absorbed by an active and saturable transport system, and has a high volume of distribution. Gabapentin is not bound to plasma proteins, does not induce hepatic enzymes and is not metabolized. At steady state, it has a half-life of 6-8 h, and is eliminated unchanged by renal route with a plasma clearance proportional to the creatinine clearance. It is devoid of significant drug-drug interactions when administered with the established AEDs or with oral contraceptives. Gabapentin used as an add-on AED significantly reduced the frequency of partial seizures and secondarily generalized tonic-clonic seizures in three large double-blind, placebo-controlled, parallel-group clinical trails. It is well tolerated, with transient somnolence and dizziness being the most frequent adverse effects. Although the mechanism of action of gabapentin is not fully established, there is strong evidence to suggest a novel mechanism of action. Gabapentin is a unique and promising drug that could improve the quality of life of patients with epilepsy and is a welcome addition to the armamentarium of currently available AEDs for the treatment of patients with seizures of partial onset.

Acetates↗

PubMed1997

Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain.

Gabapentin and S-(+)-3-isobutylgaba are anticonvulsant agents that selectively interact with the alpha2delta subunit of voltage-dependent calcium channels. This report describes the activities of these two compounds in a rat model of postoperative pain. An incision of the plantaris muscle of a hind paw induced thermal hyperalgesia and tactile allodynia lasting at least 3 days. Postoperative testing was carried out using the plantar test for thermal hyperalgesia and von Frey hairs for tactile allodynia. A single s.c. dose of gabapentin, 1 h before surgery, dose-dependently (3-30 mg/kg) blocked the development of allodynia and hyperalgesia with a minimum effective dose (MED) of 10 and 30 mg/kg, respectively. The highest dose of gabapentin prevented development of hyperalgesia and allodynia for 24 and 49 h, respectively. Similar administration of S-(+)-3-isobutylgaba also dose-dependently (3-30 mg/kg, s.c.) prevented development of hyperalgesia and allodynia with MED of 3 and 10 mg/kg, respectively. The highest dose of S-(+)-3-isobutylgaba completely blocked development of both nociceptive responses for 3 days. The administration of S-(+)-3-isobutylgaba (30 mg/kg s.c.) 1 h after surgery also completely blocked the maintenance of hyperalgesia and allodynia, but its duration of action was much shorter (3 h). The administration of morphine (1-6 mg/kg s.c.) 0.5 h before surgery prevented the development of thermal hyperalgesia with a MED of 1 mg/kg. However, unlike gabapentin and S-(+)-3-isobutylgaba, it had little effect on the development of tactile allodynia. It is suggested that gabapentin and S-(+)-3-isobutylgaba may be effective in the treatment of postoperative pain.

Acetates↗

PubMed1998

Outcome evaluation of gabapentin as add-on therapy for partial seizures. "NEON" Study Investigators Group. Neurontin Evaluation of Outcomes in Neurological Practice.

OBJECTIVE: The safety, tolerability, efficacy, and impact on quality of life of gabapentin (Neurontin) as adjunctive therapy to carbamazepine (CBZ) and/or phenytoin (PHT) was assessed in epileptic patients with partial seizures. METHODS: NEON (Neurontin Evaluation of Outcomes in Neurological Practice) was an open-label, prospective, multicentre study conducted in patients on a stable dose of CBZ and/or PHT and experiencing an average of up to 4 complex partial seizures with or without secondary generalization per month, with no seizure-free months. The treatment lasted 20 weeks. Gabapentin was started at 400 mg/day and was individually titrated to effective tolerable dose up to 2400 mg/day. Quality of life was evaluated using the QOLIE-10 questionnaire. RESULTS: A total of 141 patients were enrolled at 36 sites; 114 patients were evaluable for efficacy analyses. The mean maintenance dose of gabapentin was 1600 mg/day (range = 300-3200). A decrease of 50% or more in frequency of complex partial + secondary generalized seizures was observed in 81 (71%) patients (p = 0.0001). Fifty two (46%) patients were seizure-free during the last 8 weeks of treatment. A significant improvement (p < 0.05) was observed in 5 of the 10 questions of the QOLIE-10, as well as in the composite QOL score (p = 0.0002). The most frequent adverse events included somnolence (16%), dizziness (9%), and asthenia (6%). Twenty-five (18%) patients prematurely discontinued the study, 16 (11%) of them due to adverse events. CONCLUSIONS: This study indicates that treatment with gabapentin as adjunctive therapy to standard antiepileptic drugs in this group of patients not only provides significant improvement in seizure control, but also has a positive impact on quality of life. The clinical benefits in efficacy, safety and tolerability demonstrated at 20 weeks are sustained, and no tolerance develops with gabapentin in longer term use.

Acetates↗

PubMed1998

Cloning and deletion mutagenesis of the alpha2 delta calcium channel subunit from porcine cerebral cortex. Expression of a soluble form of the protein that retains [3H]gabapentin binding activity.

The anti-epileptic, anti-hyperalgesic, and anxiolytic agent gabapentin (1-(aminomethyl)-cyclohexane acetic acid or Neurontin) has previously been shown to bind with high affinity to the alpha2delta subunit of voltage-dependent calcium channels (Gee, N. S. , Brown, J. P., Dissanayake, V. U. K., Offord, J., Thurlow, R., and Woodruff, G.N. (1996) J. Biol. Chem. 271, 5768-5776). We report here the cloning, sequencing, and deletion mutagenesis of the alpha2delta subunit from porcine brain. The deduced protein sequence has a 95.9 and 98.2% identity to the rat and human neuronal alpha2 delta sequences, respectively. [3H]Gabapentin binds with a KD of 37.5 +/- 10.4 nM to membranes prepared from COS-7 cells transfected with wild-type porcine alpha2 delta cDNA. Six deletion mutants (B-G) that lack the delta polypeptide, together with varying amounts of the alpha2 component, failed to bind [3H]gabapentin. C-terminal deletion mutagenesis of the delta polypeptide identified a segment (residues 960-994) required for correct assembly of the [3H]gabapentin binding pocket. Mutant L, which lacks the putative membrane anchor in the delta sequence, was found in both membrane-associated and soluble secreted forms. The soluble form was not proteolytically cleaved into separate alpha2 and delta chains but still retained a high affinity (KD = 30.7 +/- 8.1 nM) for [3H]gabapentin. The production of a soluble alpha2delta mutant supports the single transmembrane model of the alpha2 delta subunit and is an important step toward the large-scale recombinant expression of the protein.

Amino Acid Sequence↗

PubMed2002

Gabapentin: new indication. In postherpetic neuralgia when amitriptyline fails.

(1) Postherpetic pain is infrequent, but the incidence increases with age. (2) The reference treatment for postherpetic pain is oral amitriptyline or desipramine. (3) Gabapentin, an antiepileptic agent, is the first drug to be granted specific approval in France for the treatment of postherpetic pain. (4) In two placebo-controlled trials, gabapentin at a dose of between 1 800 and 3 600 mg/day halved the intensity of pain in about one in three patients. In comparison, pain improved in about 50% of patients taking amitriptyline in clinical trials. (5) Both gabapentin and amitriptyline provoke sedation, but dizziness and peripheral oedema are more frequent on gabapentin, while atropinic effects predominate with amitriptyline. (6) Daily treatment is 10 times more costly in France. (7) In practice, the standard treatment of postherpetic pain remains oral amitriptyline or desipramine. Gabapentin is an alternative, given its different safety profile.

Acetates↗

PubMed2005

Design, synthesis, and preliminary evaluation of gabapentin-pregabalin mutual prodrugs in relieving neuropathic pain.

As a part of a program for the development of specific analgesics in relieving neuropathic pain, the purpose of the present study was to investigate a new concept that involves the conjugation of two drugs, gabapentin and pregabalin, as mutual prodrugs using a chemical modification approach. A series of gabapentin-pregabalin diester compounds were synthesized using linear or branch bis-hydroxyl linkers. Their pharmacological properties for treating neuropathic pain were investigated in a rat model of chronic sciatic nerve constriction injury (CCI). In-vivo evaluation demonstrated that 1a and 1b composed of two gabapentin molecules as well as 3a composed of gabapentin and pregabalin with the short linear linker, were effective in reversing tactile allodynia in CCI rats. Compounds with longer or side-branched linkers showed lower efficiencies and severe adverse effects.

Amines↗

PubMed1988

Gabapentin augments whole blood serotonin in healthy young men.

It has been previously demonstrated that gabapentin, a gamma-amino butyric acid analogue, inhibits monoaminergic neurotransmitter release from rabbit caudate nucleus slices and from rat cortex. In humans this drug has been shown to have anti-epileptogenic activity. Serotonin may act as an inhibitory neurotransmitter and its interaction with blood platelets is thought to reflect its central actions. We investigated sleep stages, whole blood serotonin levels, and serum melatonin in healthy men after the administration of gabapentin. With increasing serum gabapentin levels six healthy subjects showed an increase in sleep stages 3 and 4 and in whole blood serotonin (P less than 0.05) Serum melatonin levels were not influenced. On account of these results we speculate that gabapentin modulates the release of serotonin from blood platelets. The increase in peripheral serotonin points paradigmatically to an increase in the bioavailability of serotonin which may account for the increase in sleep stages 3 and 4.

Acetates↗

PubMed2005

Gabapentin provides effective postoperative analgesia whether administered pre-emptively or post-incision.

PURPOSE: We investigated the effects of pre-incision and post-incision administration of gabapentin on postoperative pain and fentanyl consumption associated with open donor nephrectomy. METHODS: Sixty ASA I subjects were randomly allocated into three groups to receive gabapentin 600 mg two hours before surgery and placebo after surgical incision (pre-incision group), placebo two hours before surgery and gabapentin 600 mg after surgical incision (post-incision group), or placebo two hours before surgery and after surgical incision (placebo group). After surgery, pain was assessed using a visual analogue scale (VAS), (1-10 cm) at time points 0, 6, 12, 18, and 24 hr. Subjects received patient-controlled-analgesia (fentanyl 1.0 microg x kg(-1) subject activated dose). Total fentanyl consumption in each group was recorded. RESULTS: Subjects of pre-incision and post-incision groups had lower VAS scores at all time points (3.1 +/- 1.8, 2.9 +/- 1.3, 2.8 +/- 1.3, 2.5 +/- 0.9, 2.5 +/- 1.5 and 3.6 +/- 1.1, 3.0 +/- 1.2, 3.2 +/- 1.1, 2.9 +/- 1.0, 2.6 +/- 2.2) compared to placebo group (6.6 +/- 1.3, 5.0 +/- 1.0, 4.4 +/- 0.7, 4.2 +/- 0.8, 3.9 +/- 1.0). They also used less fentanyl (563.3 microg +/- 252.8 and 624.0 microg +/- 210.5 respectively) compared to placebo (924.7 microg +/- 417.5), (P < 0.05). No difference in total fentanyl consumption and pain scores at any time points were observed between pre- and post-incision groups. CONCLUSION: Pre-incision administration of 600 mg gabapentin has no added benefit over post-incision administration in terms of pain scores and fentanyl consumption in subjects undergoing open donor nephrectomy.

Administration, Oral↗

PubMed2000

Antinociception and (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid antagonism by gabapentin in the rat spinal cord in vivo.

Gabapentin, a novel anticonvulsant and analgesic with an unknown mechanism of action, was tested on spinal dorsal horn neurone activity evoked by iontophoretically applied N-methyl-D-aspartic acid (NMDA) and (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and on nociceptive responses of single motor units (SMU) in anaesthetised rats. Gabapentin (10-215 mg/kg, i.v.) dose-dependently and selectively inhibited AMPA-evoked neuronal responses (ED50 106+/-24 mg/kg); no effect on NMDA-evoked activity was observed. In the same dose-range, gabapentin (10-215 mg/ kg, i.v.) dose-dependently reduced SMU responses to noxious electrical and mechanical stimulation. We conclude that gabapentin acts as an AMPA antagonist in the rat spinal cord, and that this mechanism is likely to substantially contribute to the antinociceptive effect of the drug.

Acetates↗

PubMed2001

Tissue-specific expression and gabapentin-binding properties of calcium channel alpha2delta subunit subtypes.

We report here the tissue-specific expression and gabapentin-binding properties of calcium channel alpha2delta subunits. Northern blot analysis demonstrated that human alpha2delta-1, -2, and -3 mRNA all had high levels of expression in brain, heart and skeletal muscle. However, the highest expression of human alpha2delta-2 mRNA was found in lung. Human alpha2delta-1, -2, and -3 mRNAs were detected in all portions of brain tested. Western blotting revealed that alpha2delta-2 protein was predominantly expressed in cerebellar cortex (brain) and undetectable in lung. The dissociation between mRNA and protein levels of human alpha2delta-2 in lung suggests possible post-transcriptional regulation. Although mouse alpha2delta-1 proteins exhibited a similar tissue distribution profile as that of human, tissue distribution of mouse alpha2delta-2 and -3 mRNA revealed a different profile. Mouse alpha2delta-3 mRNA was restricted to brain and mouse alpha2delta-2 mRNA was not detectable in lung. Gel electrophoresis under a reduced condition resulted in a mobility shift of both alpha2delta-1 and alpha2delta-2 proteins, suggesting that alpha2 and delta of alpha2delta-2 protein are linked by disulfide bond as are alpha2 and delta of alpha2delta-1. Scatchard plots revealed a single population of gabapentin binding sites for human alpha2delta-2 with the KD value twofold higher than that of porcine alpha2delta-1 (156 +/- 25 nm vs. 72 +/- 9 nm). Inhibition of gabapentin binding to alpha2delta-2 by selected amino acids and gabapentin analogs produced a binding profile similar, but not identical to that of alpha2delta-1.

Acetates↗

PubMed2006

The effect of gabapentin in earlier stage of reflex sympathetic dystrophy.

The objective of this paper is to investigate the effect of gabapentin in the earlier stage of reflex sympathetic dystrophy syndrome (RSD). Twenty-two patients diagnosed with RSD were enrolled. Initial gabapentin dosage was 600 mg/day. This dosage is increased gradually until a satisfactory pain level was reached. After this level, this dosage was maintained throughout the study. An exercise program was also applied to the patients. Provoked and static pain scores of the patients were obtained initially, at 3-day intervals for maintenance dosage determining, and at 6 weeks after the discharge. Functional improvement parameters were volumetric measurement; dynamometric measurement and third finger pulp-distal palmar crease distance measurement for hands; and metric circumferential measurement and range of motion for elbow, knee, and foot initially, at baseline, on the tenth day, upon discharge, and 6 weeks after the discharge. The mean maintenance dose of gabapentin was 1,145.46+/-377.6 mg/day (range, 900-1,800 mg/day). Improvements in spontaneous and provoked pain intensities were statistically significant. No statistically significant difference was obtained in functional improvement parameters. Dizziness in three patients, headache in two patients, and mild burning feeling in the tongue in one patient were the reported side effects. These symptoms resolved spontaneously in few days. Gabapentin cannot be recommended as the drug of choice, but it may be considered as one of the therapeutic alternatives in the management of pain due to RSD. We suggest that it is effective only for the pain and not for other symptoms of RSD. Serious side effects that will cause the patient to stop using the drug are rare.

Adult↗

PubMed2001

Modification of cortical excitability induced by gabapentin: a study by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) was employed before and after a single dose of gabapentin to evaluate how this drug affects the activity of excitatory and inhibitory circuits within the motor cortex. Eleven healthy volunteers were studied. For the evaluation of cortical excitability, the following parameters were taken into account: resting and active motor threshold (RMT, AMT); cortical silent period (CSP); and intracortical inhibition (ICI) and facilitation (ICF). Peripheral silent period (PSP) was also detected. All parameters were measured before and 3 and 24 hours after 800 mg gabapentin was administered in a single oral dose. Gabapentin deepened the ICI and suppressed the ICF at 3 h but not at 5 h after dosing. We conclude that, in the normal human brain, gabapentin may act on intracortical excitability by shifting the balance towards less excitation and more inhibition.

Acetates↗

PubMed1996

Determination of gabapentin in plasma by high-performance liquid chromatography.

A rapid and simple method for determination of the novel antiepileptic compound gabapentin [1-(aminomethyl)cyclohexaneacetic acid] in plasma is described. Blank human plasma was spiked with gabapentin (1.0-10.0 micrograms/ml) and internal standard [1-(aminomethyl)-cycloheptaneacetic acid; 5.0 micrograms/ml]. Individual samples were treated with 2 M perchloric acid, centrifuged and then derivatised with o-phthalaldehyde-3-mercaptopropionic acid. Separation was achieved on a Beckman Ultrasphere 5 microns reversed-phase column with mobile phase consisting of 0.33 M acetate buffer (pH 3.7; containing 100 mg/l EDTA)-methanol-acetonitrile (40:30:30, v/v). Eluents were monitored by fluorescence spectroscopy with excitation and emission wavelengths of 330 and 440 nm, respectively. The calibration curve for gabapentin in plasma was linear (r = 0.9997) over the concentration range 1.0-10.0 micrograms/ml. Recovery was seen to be > or = 90%. The inter- and intra-assay variations for three different gabapentin concentrations were < or = 10% throughout. The lower limit of quantitation was found to be 0.5 microgram/ml. Chromatography was unaffected by a range of commonly employed antiepileptic drugs or selected amino acids.

Acetates↗

PubMed2004

Effect of K+ channel modulators on the antiallodynic effect of gabapentin.

The effect of K+ channel inhibitors on the antiallodynic activity induced by spinal gabapentin was assessed in rats. Ligation of L5 and L6 spinal nerves made the rats allodynic, whereas that intrathecal administration of gabapentin (25-200 microg) reduced tactile allodynia in a dose-dependent manner. Spinal pretreatment with glibenclamide (12.5-50 microg, ATP-sensitive K+ channel inhibitor), charybdotoxin (0.01-1 ng) or apamin (0.1-3 ng, large-and small-conductance Ca2+-activated K+ channel blockers, respectively), but not margatoxin (0.01-10 ng, voltage-dependent K+ channel inhibitor), significantly prevented gabapentin-induced antiallodynia. Pinacidil (1-30 microg, K+ channel opener) significantly reduced nerve ligation-induced allodynia. Intrathecal glibenclamide (50 microg), charybdotoxin (1 ng) and apamin (3 ng), but not margatoxin (10 ng), significantly reduced pinacidil-induced antiallodynia. K+ channel inhibitors alone did not modify allodynia produced by spinal nerve ligation. Results suggest that gabapentin and pinacidil may activate Ca2+-activated and ATP-sensitive K+ channels in order to produce part of its spinal antiallodynic effect in the Chung model.

Acetates↗

PubMed2004

Gabapentin activates presynaptic GABAB heteroreceptors in rat cortical slices.

In electrically stimulated rat neocortical brain slices preloaded with [3H]gamma-aminobutyric acid (GABA) or [3H]glutamic acid, the pharmacological actions of 1-(aminomethyl)-cyclohexaneacetic acid (gabapentin, Gp) were compared with the GABAB receptor agonists baclofen (Bac) and (3-amino-2-(S)-hydroxypropyl)-methylphosphinic acid (CGP 44532). Gabapentin, baclofen and CGP 44532 all reduced the electrically stimulated release of [3H]glutamic acid (IC50=20 microM, 0.8 microM and 2 microM, respectively). These effects were sensitive to the GABAB receptor antagonists (+)-(S)-5,5 dimethylmorpholinyl-2-acetic acid (Sch 50911) or N-3-[[1-(S)-(3,4-dichlorophenyl)ethyl]amino]-2-(S)-hydroxypropyl-P-(cyclo-hexylmethyl)-phosphinic acid (CGP 54626). By contrast, gabapentin was without effect on the release of [3H]GABA, whilst baclofen (IC50=8 microM) and CGP 44532 (IC50=1 microM) inhibited [3H]GABA release. It is concluded that gabapentin selectively activates presynaptic GABAB heteroreceptors, but not GABAB autoreceptors, and may be a useful ligand to discriminate between presynaptic GABAB receptor subtypes.

Amines↗

PubMed2005

Synergistic interaction of gabapentin and oxcarbazepine in the mouse maximal electroshock seizure model--an isobolographic analysis.

The anticonvulsant effects produced by mixtures of oxcarbazepine and gabapentin (two second-generation antiepileptic drugs) in numerous fixed-ratio combinations of 1:1, 1:2, 1:5, 1:10, 1:15, and 1:20 were examined isobolographically in the mouse maximal electroshock seizure model. Results displayed that mixtures of both drugs at the fixed-ratios of 1:2, 1:5, 1:10, 1:15, and 1:20 exerted supra-additive (synergistic) interactions against electroconvulsions. Only a fixed-ratio of 1:1 was indifferent with isobolography, although the combination displayed the trend towards supra-additivity. Furthermore, the combinations of oxcarbazepine with gabapentin, administered at their median effective doses (ED(50 mix)s), did not alter motor performance of animals challenged with the chimney test. Additionally, neither gabapentin nor oxcarbazepine affected total brain concentrations of co-administered drug, indicating a pharmacodynamic nature of interaction between these antiepileptics. Finally, based on preclinical data presented here the combination of oxcarbazepine and gabapentin is of particular importance for further therapy in patients with refractory partial seizures.

Amines↗