Gabapentin Research Articles

Transfer Mechanisms of Compounds between Mother and Fetus/Infant Aimed for Optimized Medication during Pregnancy and Breastfeeding

Potential risks to the fetus or infant should be considered prior to medication during pregnancy and lactation. It is essential to evaluate the exposure levels of drugs and their related factors in addition to toxicological effects. Epilepsy is one of the most common neurological complications in pregnancy; some women continue to use antiepileptic drugs (AEDs) to control seizures. Benzodiazepines (BZDs) are widely prescribed for several women who experience symptoms such as anxiety and insomnia during the postpartum period. In this review, we describe the 1) transport mechanisms of AEDs across the placenta and the effects of these drugs on placental transporters, and 2) the transfer of BZDs into breast milk. Our findings indicated that carrier systems were involved in the uptake of gabapentin (GBP) and lamotrigine (LTG) in placental trophoblast cell lines. SLC7A5 was the main contributor to GBP transport in placental cells. LTG was transported by a carrier that was sensitive to chloroquine, imipramine, quinidine, and verapamil. Short-term exposure to 16 AEDs had no effect on folic acid uptake in placental cells. However, long-term exposure to valproic acid (VPA) affected the expression of folate carriers (FOLR1, SLC46A1). Furthermore, VPA administration changed the expression levels of various transporters in rat placenta, suggesting that sensitivity to VPA differed across gestational stages. Lastly, we developed a method for quantifying eight BZDs in human breast milk and plasma using LC/MS/MS, and successfully applied it to quantify alprazolam in breast milk and plasma donated by a lactating woman.

Baclofen: To Screen or Not to Screen in Postmortem Blood?

Baclofen (BLF) has been prescribed in the UK since 1972 for the alleviation of spasticity. However, evidence suggests BLF is also recreationally misused. It has been associated with ethanol, gamma-hydroxybutyric acid (GHB), pregabalin (PGL) and gabapentin (GBP) use/abuse, and deaths have been reported. With current postmortem (PM) toxicological screening approaches, BLF is not routinely included in the general drugs screen and is only screened for if specifically mentioned in the case documents. The extent of BLF misuse is thus unclear. This study was carried out to determine the prevalence and concentrations of BLF in Coroners' toxicology, to investigate whether BLF misuse with ethanol, GHB, PGL and GBP is causing death and to determine the potential extent of the underreporting of BLF-associated deaths. Between 1 January 2016 and 31 December 2017, 3,750 PM femoral vein bloods were screened for BLF; all positive cases were quantified. Only 0.56% of samples screened positive for BLF, with concentration ranging from 0.08 to 102.00 µg/mL (median = 0.28). It was determined that if routine analysis without additional screening of BLF had been performed, 43% of BLF positives cases would have been missed. However, given the low incidence of detection, this only represents 0.25% of the cohort. Likely illicit use of BLF with GHB was seen in one case only. Death from the recreational use of BLF with PGL and GBP was not observed. Only two cases positive for BLF had an ethanol concentration of ≥50 mg%. Two cases of presumed intentional overdose of BLF were observed. This study highlights that although BLF abuse may be occurring, deaths are rare. It is therefore not cost- or time-effective to screen for BLF in all PM cases. With BLF currently being investigated for the treatment of alcoholism and withdrawal symptoms of illicit drug use, BLF-related deaths may rise in the future.

Lamotrigine and gabapentin ameliorate neurotoxicity induced by lipopolysaccharide in mice

Background: Alzheimer’s disease (AD), the most common cause for dementia, is an irreversible progressive neurodegenerative disorder. Aim: To investigate the potential protective role of Lamotrigine (LTG) and Gabapentin (GBP) either alone and in combination in Lipopolysaccride-induced Alzheimer's disease (AD) in mice. Materials and Methods: Mice were divided into 5 groups: Normal control group, Lipopolysaccride (LPS) group (animals were injected by single I.P. dose of LPS in a dose of 0.8 mg/kg), LTG group (animals were injected by single I.P. dose of LPS 0.8 mg/kg and received oral LTG 30 mg/kg/day), GBP group (animals were injected by single I.P. dose of LPS 0.8 mg/kg and received oral GBP 200 mg/kg/day) and LTG+GBP group (animals were injected by single I.P. dose of LPS 0.8 mg/kg and received both oral LTG 30 mg/kg/day and GBP 200 mg/kg/day), therapy started 2-h after LPS injection for 7 successive days. Novel object recognition and Y-maze tests were conducted. Brain homogenate used for the estimation of superoxide dismutase (SOD), acetylcholine esterase (AchE) activity, glutamate, reduced glutathione (GSH) and malonyialdehyde (MDA) contents. Results: LPS significantly induced neurobehavioral disturbances compared to normal control with significantly higher MDA, AchE and glutamate contents, with a reduction in SOD and GSH levels. Treatment with either LTG or GBP significantly ameliorated the effects of LPS injection on neurobehavioral tests, oxidative milieu with a significant reduction in AchE activity and glutamate content in favor of LTG. Combined therapy significantly improved both neurobehavioral testing and the estimated biochemical markers. Conclusion: GBP and/or LTG therapy improved neurobehavioral testing in LPS- induced AD in mice by restoring oxidant/antioxidant milieu with a concomitant reduction in AchE activity and glutamate content. Furthermore; the combination of both drugs resulted in significant improvement than either one of them alone that merits further clinical investigation.

Synthesis of Novel Gabapentin Scaffold Derived Hydrazide-hydrazones for Potential Antimicrobial agents and Antioxidants

Twelve new analogues of gabapentin (GBP) derived hydrazide-hydrazone scaffolds were produced by using various electronically and structurally divergent aromatic aldehydes. All the hydrazones were obtained in moderate to good yields (66–82%) by heating the GBP hydrazide with respective aldehydes to a temperature of 45–65 °C for 4–7 h. Further, the compounds were explored for their antimicrobial activity on three different Gram positive (Micrococcus luteus, Streptococcus mutans, Enterococcus faecalis) and Gram negative bacterial strains (Salmonella enterica, Alcaligenes faecalis, Pseudomonas aeruginosa). The antibacterial results obtained were found to be good against Gram positive bacteria when compared to Gram negative bacteria. Moreover, the compounds were also screened for antioxidant activity at four different concentrations using the DPPH method and the results showed that some of the compounds were moderately active.

Gabapentin Inhibits Multiple Steps in the Amyloid Beta Toxicity Cascade

Oligomeric β-amyloid peptide (Aβ) is one of the main neurotoxic agents of Alzheimer's disease (AD). Oligomers associate to neuronal membranes, forming "pore-like" structures that cause intracellular calcium and neurotransmitter dyshomeostasis, leading to synaptic failure and death. Through molecular screening targeting the C terminal region of Aβ, a region involved in the toxic properties of the peptide, we detected an FDA approved compound, gabapentin (GBP), with neuroprotective effects against Aβ toxicity. At micromolar concentrations, GBP antagonized peptide aggregation over time and reduced the Aβ absorbance plateau to 28% of control. In addition, GBP decreased Aβ association to membranes by almost half, and the effects of Aβ on intracellular calcium in hippocampal neurons were antagonized without causing effects on its own. Finally, we found that GBP was able to block the synaptotoxicity induced by Aβ in hippocampal neurons, increasing post-synaptic currents from 1.7 ± 0.9 to 4.2 ± 0.7 fC and mean relative fluorescence intensity values of SV2, a synaptic protein, from 0.7 ± 0.09 to 1.00 ± 0.08. The results show that GBP can interfere with Aβ-induced toxicity by blocking multiple steps, resulting in neuroprotection, which justifies advancing toward additional animal and human studies.

<p>The Use of Gabapentin for the Treatment of Alcohol and Tobacco Use Disorders: A Review</p>

<p>The Use of Gabapentin for the Treatment of Alcohol and Tobacco Use Disorders: A Review</p>

Comparison of gabapentin and hydroxyzine in the treatment of pruritus in patients on dialysis

Pruritus is one of the most common problems in patients with chronic renal failure. Of all patients with end-stage renal disease (ESRD), 60-80% report pruritus during their life. To compare the effect of gabapentin (GBP) and hydroxyzine (HYDZ) in treating pruritus in patients on dialysis. In a double-blind, randomized, crossover clinical trial, 32 patients on dialysis who reported pruritus were assigned randomly to receive either GBP or HYDZ for 6weeks; the first group received GBP 100mg/day orally and the second group received HYDZ 25mg/day orally for 6weeks. After this 6-week period (Period 1) there was a washout period of 2weeks then patients were crossed over to the other drug (the first group receiving HYDZ and second group receiving GBP) and followed up for a further 6weeks (Period 2). A visual analogue scale was used to measure pruritus intensity in the groups before and after the first and second period. In Period 1, pruritus severity decreased from 7.1±1.46 at baseline to 2.17±1.82 at 6weeks in the GBP group (P=0.001) and from 6.83±2.11 to 2.86±1.67 in the HYDZ group (P=0.001). In Period 2, pruritus severity decreased from 5.1±1.61 at baseline to 1.56±0.82 at 6weeks in the GBP group (P<0.01) and from 5.23±2.11 to 2.1±1.87 in the HYDZ group (P=0.001). Results showed that both HYDZ and GBP significantly improved and controlled pruritus in patients on dialysis, with no significant difference observed between the two drugs.

Gabapentinoids for Perioperative Pain

Gabapentinoids (gabapentin and pregabalin) are prescribed widely for perioperative pain management, in part to reduce opioid use after surgery. Now,

Assessment of the biotic and abiotic elimination processes of five micropollutants during cultivation of the green microalgae Acutodesmus obliquus

The elimination by photolysis, microalgae and sorption of five persistent micropollutants Sulfamethoxazole (SMX), Ciprofloxacin (CIP), Quetiapine (QUT), Gabapentin (GAB) and 2-Phenyl-5-benzimidazolesulfonic acid (PBSA) was studied. Microalgae growth was not inhibited by the micropollutants. SMX, QUT, CIP were significantly eliminated during exposure with microalgae, while GAB and PBSA remained unaffected. SMX was eliminated by 43% only under optimal cultivation conditions at an elimination rate of 2.1 μg L−1 h−1. Sorption and photolysis were not involved in the elimination of SMX. QUT was eliminated by 99% with a rate of 4.6 μg L−1 h−1 during microalgae cultivation as a result of photolysis and microalgae activity. Microalgae cultivation produced a 52.8% higher elimination compared photolysis. CIP decreased by 86% at a rate of 1.78 μg L−1 h−1 which was mainly produced by photolysis with an impact of microalgae of 10%. Growth rates of the microalgae and elimination rates of the micropollutants were not correlating. While the underlying processes remained unclear, present study shows that biotic processes coupled to the growth of Acutodesmus obliquus removed most of the micropollutants under study at rates exceeding those of the abiotic removal processes.

Gabapentinoids for treatment of alcohol use disorder: A systematic review and meta-analysis.

Gabapentin (GBP) and pregabalin (PGB) have been used to treat alcohol use disorder (AUD) and alcohol withdrawal, but with inconsistent results. In this meta-analysis, we explored the effects of GBP/PGB treatment on AUD and their effects on withdrawal, craving, depression, and sleep disturbance in AUD patients. We carried out a systematic review and meta-analysis of randomized controlled trials comparing the effects of GBP/PGB on AUD with those of a placebo or control treatment. Electronic databases were searched for relevant articles published before September 2019. The primary outcome was defined as the efficacy measure on achieving abstinence or reducing alcohol consumption in a hierarchical order. We included 16 studies in our meta-analysis. Overall, GBP had no significant benefit comparing to placebo or control treatment (Hedges' g = 0.0725, p = 0.6743). For specific alcohol-related outcome, GBP had significant effect on percentage of heavy drink (Hedges' g = 0.5478, p = 0.0441) and alcohol withdrawal symptoms (Hedges' g = 0.2475, p = 0.0425). GBP/PGB did not have significant beneficial effect on craving, depressive symptoms, or sleep disturbance. Instability was shown in sensitivity analyses of some above results. GBP may be helpful to reduce AUD patients' heavy drinking behavior and withdrawal, but more studies are needed for drawing conclusions.

Pyrrolidin-2-one linked benzofused heterocycles as novel small molecule monoacylglycerol lipase inhibitors and antinociceptive agents.

Eighteen pyrrolidin-2-one linked benzothiazole, and benzimidazole derivatives (10-27) were designed and synthesized. The structure of the compounds was confirmed by elemental and spectral (IR, 1 H-NMR and MS) data analysis. All the compounds were screened by human monoacylglycerol lipase (hMAGL) inhibition assay. Three benzimidazole compounds, 22 (4-Cl phenyl), 23 (3-Cl,4-F phenyl) and 25 (4-methoxy phenyl) were found to be the most potent, having an IC50 value of 8.6, 8.0 and 9.4nm, respectively. Among them, the halogen-substituted phenyl derivatives, compound 22 (4-Cl phenyl) and compound 23 (3-Cl,4-F phenyl), showed micromolar potency against fatty acid amide hydrolase (FAAH), having an IC50 value of 35 and 24µm, respectively. Benzimidazole derivative having 4-methoxyphenyl substitution (compound 25) was found to be a selective MAGL inhibitor (IC50 =9.4nm), with an IC50 value above 50µm against FAAH. In the formalin-induced nociception test, compound 25 showed a dose-dependent reduction of pain response in both acute and late phases. At 30mg/kg dose, it significantly reduced the pain response and showed greater potency than the reference drug gabapentin (GBP).

Occurrence and transformation of gabapentin in urban water quality engineering: Rapid formation of nitrile from amine during drinking water chlorination

The occurrence and fate of the popular pharmaceutical gabapentin (GBP) in the urban water cycle were investigated with a focus on its transformation during water chlorination. GBP was detected in all samples with average concentrations of 1285 ng/L (n = 24) for wastewater effluent, 304 ng/L for river water (n = 22), and 180 ng/L for drinking water treatment plant (DWTP) influent (n = 4). The monitoring sites were located in the Nakdong River watershed, Korea. GBP was rapidly (within 20 min) transformed into 1-cyanocyclohexylacetic acid (GBP-nitrile) under typical chlorination conditions (1.4 mgCl2/L). When there was a molar excess of chlorine to GBP, the primary amine of GBP was double-chlorinated to form N-Cl2 GBP with a second-order rate constant of >103 M−1 s−1. Decomposition of N-Cl2 GBP had a first-order rate constant of (0.5–1.0) × 10−2 s−1 and produced GBP-nitrile with a yield of 87%–100%. We propose that N-Cl2 GBP is transformed into N-Cl GBP imine and then to GBP-nitrile via two consecutive dehydrochlorinations with the former as the rate-limiting step. N-Cl2 GBP had a much higher decomposition rate than N-Cl2 produced from other simple aliphatic amines, which could be related to the structural features of GBP such as its carboxyl group and quaternary β-carbon. The wastewater effluent samples did not contain GBP-nitrile even in the chlorinated effluent because of the relatively low chlorine dose or high ammonia level. In a full-scale DWTP employing a pre-chlorination unit, GBP present in the influent river water was fully transformed into GBP-nitrile. The formed GBP-nitrile was degraded in subsequent ozonation (•OH oxidation) and biological activated carbon filtration (biodegradation) processes. The toxicity of GBP-nitrile is thought to be low but further studies are warranted to assess the toxicological relevance of nitrile formation during water chlorination.

Effect of Glucose Cometabolism on Biodegradation of Gabapentin (an Anticonvulsant Drug) by Gram-Positive Bacteria Micrococcus luteus N.ISM.1

A gram-positive gabapentin-degrading bacteria strain N.ISM.1 was isolated from the pharmaceutical plant soil. According to the analysis of 16S rRNA gene sequence, the strain was categorized as a Micrococcus luteus. Though the strain N.ISM.1 is capable of degrading gabapentin (GABA), this compound cannot provide enough carbon source for the isolated strain. M. luteus N.ISM.1 degrades GABA in the presence of glucose. The greater the concentration of secondary simpler carbon source (glucose) for cometabolism, the greater the biodegradation of GABA is. Around 97% of GABA was degraded within a course of 40 days after using 150 mg/L glucose as cometabolic simpler carbon source. M. luteus N.ISM.1 is a promising microorganism for the biodegradation of an anticonvulsant drug GABA contaminated environment and with the aid of cometabolic activity of glucose (150 mg/L) the degradation achieved perfection. GABA biodegradation metabolites were identified by a liquid chromatography-electrospray ionization tandem mass spectrometry. This is the very first report of GABA biodegradation as per our concern.

Unilateral Oculomotor Nerve Dysfunction Induced by Ruptured Anterior Communicating Artery Aneurysm along with Isolated Intraventricular Hemorrhage in a Trauma Patient

Background: Many signs in relation to vascular events and consequent loss of consciousness could be easily incorrectly explained (unclear) in a setting of trauma, especially when these events are a result of the car accident. Third cranial nerve palsy widely occurs due to internal carotid and posterior communicating artery aneurysm. An anterior communicating(ACOM) aneurysm is a rare reason that could lead to oculomotor dysfunction. ACOM ruptured aneurysm may present with sub arachnoid hemorrhage (SAH) and intraventricular hemorrhage (IVH) but isolated IVH is a rare finding for ACOM ruptured aneurysm. Case Description: A 56-year-old male presented to the hospital emergency department because of trauma after a car accident. He was unconscious with left-sided dilated pupil and ptosis with a brain CT indicating IVH. Brain CT angiography that performed two weeks after the accident revealed ACOM aneurysm. The patient underwent craniotomy and clipping the aneurysm. He was discharged, after completing the period of the following treatmentA combination of neuropathic agents and opioids helped to control pain. These analgesic included amitriptyline, gabapentin, pregabalin, tramadol and morphine in various regimens. Paracetamol and ibuprofen were also used. Conclusion: This report is a unique case of synchronization of third cranial nerve palsy and isolated IVH without SAH due to ACOM aneurysm. In addition, it could be interesting to re-emphasize the need for a comprehensive assessment of traumatic patients for finding some primary pathologies, which could result in an accident.

Gabapentin-induced drug-seeking-like behavior: a potential role for the dopaminergic system

Drugs of abuse represent a growing public health crisis. Accumulating evidence indicates that gabapentin (GBP), a prescription drug, is prone to misuse, abuse, withdrawal, and dependence. Commonly, drugs of abuse modulate the dopaminergic system to induce addiction. In this study, we used the conditioned place preference (CPP) model to investigate the involvement of the dopamine 1 (D1) receptor on the reward and reinforcement behavior of GBP. Under a CPP paradigm, male BALB/c mice were intraperitoneally injected either saline or 100, 200, or 300 mg/kg of GBP and confined to the injection-paired chamber for 30 min. In the pre-conditioning phase, mice were conditioned for 3 days, and baseline data were collected. In the conditioning phase, mice were given once-daily alternating injections of either GBP or saline for 8 days and subsequently assessed in a post-conditioning test. Injections of 300 mg/kg of GBP significantly increased the time spent in the drug-paired chamber compared to the saline-paired chamber. However, lower doses of GBP (100 and 200 mg/kg) showed no effect. Pre-treatment with SKF-83566, a D1 receptor antagonist, attenuated GBP-induced CPP. Thus, for the first time, we show that GBP can induce CPP through a dopaminergic-dependent mechanism.

Polygonogram and isobolographic analysis of interactions between various novel antiepileptic drugs in the 6-Hz corneal stimulation-induced seizure model in mice.

Pharmacotherapy with two antiepileptic drugs in combination is usually prescribed to epilepsy patients with refractory seizures. The choice of antiepileptic drugs in combination should be based on synergistic cooperation of the drugs with respect to suppression of seizures. The selection of synergistic interactions between antiepileptic drugs is challenging issue for physicians, especially, if 25 antiepileptic drugs are currently available and approved to treat epilepsy patients. The aim of this study was to determine all possible interactions among 5 second-generation antiepileptic drugs (gabapentin (GBP), lacosamide (LCM), levetiracetam (LEV), pregabalin (PGB) and retigabine (RTG)) in the 6-Hz corneal stimulation-induced seizure model in adult male albino Swiss mice. The anticonvulsant effects of 10 various two-drug combinations of antiepileptic drugs were evaluated with type I isobolographic analysis associated with graphical presentation of polygonogram to visualize the types of interactions. Isobolographic analysis revealed that 7 two-drug combinations of LEV+RTG, LEV+LCM, GBP+RTG, PGB+LEV, GBP+LEV, PGB+RTG, PGB+LCM were synergistic in the 6-Hz corneal stimulation-induced seizure model in mice. The additive interaction was observed for the combinations of GBP+LCM, GBP+PGB, and RTG+LCM in this seizure model in mice. The most beneficial combination, offering the highest level of synergistic suppression of seizures in mice was that of LEV+RTG, whereas the most additive combination that protected the animals from seizures was that reporting additivity for RTG+LCM. The strength of interaction for two-drug combinations can be arranged from the synergistic to the additive, as follows: LEV+RTG > LEV+LCM > GBP+RTG > PGB+LEV > GBP+LEV > PGB+RTG > PGB+LCM > GBP+LCM > GBP+PGB > RTG+LCM.

0802 To Examine the Effect of Gabapentin Enacarbil in Primary Restless Legs Syndrome Patients Who are on Dopaminergic Agents and Exhibiting Augmentation

Abstract Introduction Augmentation is defined as worsening of the symptoms of Restless Legs Syndrome after a brief period of initial improvement with dopaminergic agents resulting in either an earlier onset, increase in severity, quicker onset, spread to other body parts. The exact prevalence of this phenomenon is not known and in patients experiencing augmentation, it can pose a difficult diagnostic and therapeutic challenge to the clinician. In our study, we found extended-release gabapentin to be an effective intervention in patients experiencing dopaminergic augmentation Methods This is an open-label single-arm study done in patients exhibiting augmentation while on dopaminergic agents. Patients who were enrolled in the study were initiated on oral extended-release gabapentin(Horizont) 600 mg at 5 pm at the beginning of the study. At day 90, attempts were made to reduce or discontinue dopaminergic agents. International Restless Legs Syndrome-Rating Scale (IRLS) and Augmentation Severity Rating Scale(ASRS) were recorded at each visit. Results A total of 10 patients were enrolled in the study while only 8 patients completed it. Compared to the baseline (visit 2), there is a significant improvement in both the augmentation severity(p= 0.0131) and the IRLS (p=0.0497). Wilcoxon matched-pairs signed rank test was used for statistical analysis. Conclusion Extended-release Gabapentin is an effective treatment option in primary RLS patients experiencing augmentation secondary to dopaminergic medication usage. Support The study is funded and medication is provided by Arbor Pharmaceuticals.

Prolonged prophylactic effects of gabapentin on status epilepticus-induced neocortical injury

Long-term consequences of status epilepticus (SE) occur in a significant proportion of those who survive the acute episode. We developed an in vivo model of acute focal neocortical SE (FSE) to study long-term effects on local cortical structure and function and potential strategies to mitigate adverse consequences of SE. An acute 2 h episode of FSE was induced in anesthetized mice by epidural application of gabazine +4-aminopyridine over sensorimotor neocortex. Ten and 30 days later, the morphological and functional consequences of this single episode of FSE were studied using immunocytochemical and electrophysiological techniques. Results, focused on cortical layer V, showed astrogliosis, microgliosis, decreased neuronal density, and increased excitatory synapses, along with increased immunoreactivity for thrombospondin 2 (TSP2) and α2δ-1 proteins. In addition, neocortical slices, obtained from the area of prior focal seizure activity, showed abnormal epileptiform burst discharges along with increases in the frequency of miniature and spontaneous excitatory postsynaptic currents in layer V pyramidal cells, together with decreases in both parvalbumin immunoreactivity (PV-IR) and the frequency of miniature inhibitory postsynaptic currents in layer V pyramidal cells. Treatment with an approved drug, gabapentin (GBP) (ip 100 mg/kg/day 3×/day for 7 days following the FSE episode), prevented the gliosis, the enhanced TSP2- and α2δ-1- IR and the increased excitatory synaptic density in the affected neocortex. This model provides an approach for assessing adverse effects of FSE on neocortical structure and function and potential prophylactic treatments.

Combination Therapy of Gabapentin and N-Acetylcysteine Against Posttraumatic Epilepsy in Rats.

Traumatic brain injury (TBI) is a major public health problem worldwide that is associated with increased mortality and morbidity. Posttraumatic epilepsy (PTE) is one of the sequelae of TBI. The aim of this study was to investigate the role of N-acetylcysteine (NAC) as an adjuvant on the efficacy of levetiracetam (LEV) and gabapentin (GBP) in PTE model encouraged by pentylenetetrazol (PTZ) after mild-TBI in male Sprague-Dawley rats. Mild-TBI was performed by the weight-drop method in male Sprague-Dawley rats. PTE model was developed by injecting PTZ (30+15+15mg/kg, 30min intervals, i.p.) 7days after head trauma. After the development of posttraumatic seizures, the rats were treated with NAC (100mg/kg), LEV (50mg/kg), GBP (100mg/kg), NAC+LEV and NAC+GBP intraperitoneally for 14days. Seizures related to PTE were scored by video-EEG recording. Motor performance of the animals was also evaluated in the rotarod test. 50mg/kg LEV and 100mg/kg GBP reduced seizures related to PTE. LEV alone (p = 0.009), but the administration of GBP+NAC (p = 0.015) was more effective on PTE-related seizure control. However, GBP+NAC application adversely affected the fall latency in the rotarod test. In terms of trauma-related seizure control, there was no statistically significant difference between the use of prophylactic LEV and symptomatic LEV. LEV alone or the combination of GBP with NAC provides more effective seizure control in the PTE facilitated by PTZ. On the other hand, the use of prophylactic LEV did not have any extra effect on posttraumatic seizure development and control.

Perioperative Gabapentin or Pregabalin with Elective Orthopedic Surgery

Increasingly, surgeons are prescribing gabapentin or pregabalin to prevent or relieve postoperative pain, with the intent of limiting postoperative