Low single dose gabapentin does not affect prefrontal and occipital gamma-aminobutyric acid concentrations

The γ-aminobutyric acid (GABA) system has been proposed as a target for novel antidepressant and anxiolytic treatments. Emerging evidence suggests that gabapentin (GBP), an anticonvulsant drug that significantly increases brain GABA levels, is effective in the treatment of anxiety disorders. The current study was designed to measure prefrontal and occipital GABA levels in medication-free healthy subjects after taking 0 mg, 150 mg and 300 mg GBP. Subjects were scanned on a 3T scanner using a transmit-receive head coil that provided a relatively homogenous radiofrequency field to obtain spectroscopy measurement in the medial prefrontal (MPFC) and occipital cortex (OCC). There was no dose-dependent effect of GBP on GABA levels in the OCC or MPFC. There was also no effect on Glx, choline or N-acetyl-aspartate concentrations. The previously reported finding of increased GABA levels after GBP treatment is not evident for healthy subjects at the dose of 150 and 300 mg. As a result, if subjects are scanned on a 3T scanner, low dose GPB is not useful as an experimental challenge agent on the GABA system.     

Gabapentin Withdrawal Syndrome in a Post–Liver Transplant Patient

ABSTRACT

A 41-year-old male with a previous orthotopic liver transplant began experiencing insomnia, anxiety, diaphoresis, headaches, and palpitations that progressed over a 2-day period. As part of his home medication regimen, the patient was taking gabapentin for peripheral neuropathy. His acute onset of increasing symptoms coincided with an inadvertent discontinuation of gabapentin. After reinitiation of gabapentin therapy, the symptoms slowly improved over the next 24 hours and the episode of gabapentin withdrawal syndrome resolved.     

Gabapentin is not a GABAB receptor agonist.

Recent experiments have demonstrated that formation of functional type B gamma-aminobutyric acid (GABA_B) receptors requires co-expression of two receptor subunits, GABA_B1 and GABA_B2. Despite the identification of these subunits and a number of associated splice variants, there has been little convincing evidence of pharmacological diversity between GABA_B receptors comprising different subunit combinations. However, Ng et al. [Mol. Pharmacol., 59 (2000) 144] have recently suggested a novel and important pharmacological difference between GABA_B receptor heterodimers expressing the GABA_B1a and GABA_B1b receptor subunits. This study suggested that the antiepileptic GABA analogue gabapentin (Neurontin) is an agonist at GABA_B receptors expressing the GABA_B1a but not the GABA_B1b receptor subunit. The importance of this finding with respect to identifying novel GABA_B receptor subunit specific agonists prompted us to repeat these experiments in our own [³⁵S]−GTPγS binding and second messenger assay systems. Here we report that gabapentin was completely inactive at recombinant GABA_B heterodimers expressing either GABA_B1a or GABA_B1b receptor subunits in combination with GABA_B2 receptor subunits. In addition, in both CA1 and CA3 pyramidal neurones from rodent hippocampal slices we were unable to demonstrate any agonist-like effects of gabapentin at either pre- or post-synaptic GABA_B receptors. In contrast, gabapentin activated a GABA_A receptor mediated chloride conductance. Our data suggest that gabapentin is not a GABA_B-receptor agonist let alone a GABA_B receptor subunit selective agonist.     

Behavioral effects of agents active at the γ-aminobutyric acid receptor complex in the staircase paradigm

This study examined the behavioral effects of agents active at the γ-aminobutyric acid (GABA_A) receptor complex in the mouse staircase paradigm. The neuroactivesteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were compared with the benzodiazepine agonist clonazepam, the non-benzodiazepine hypnotic compound zopiclone, and the antiepileptic agent gabapentin. Clonazepam, zopiclone and gabapentin reduced rearing activity at doses that did not affect climbing. The rearing-suppression effect of clonazepam and zopiclone, but not of gabapentin, was blocked by the benzodiazepine antagonist flumazenil, suggesting that the added effect of gabapentin is not mediated by the benzodiazepine receptor on the GABA complex. DHEA suppressed rearing behavior at doses that did not reduce climbing, but analysis with the Bonferroni post hoc test yielded no statistically significant difference. This inhibitory effect was attenuated by flumazenil. By contrast, DHEA-S suppressed, in a dose-dependent manner, both rearing and climbing behavior to the same extent. The findings support the potential value of the mouse staircase paradigm for demonstrating behaviorally relevant anxiolysis of test compounds shown to interact in vitro with the GABA_A receptor complex.     

盐酸羟考酮控释片联合加巴喷丁治疗癌性神经性疼痛疗效分析

目的：观察盐酸羟考酮控释片联合加巴喷丁治疗癌症神经病理性疼痛的疗效及不良反应。方法：单药组盐酸羟考酮控释20 mg/片，口服每12 h 1次。联合组盐酸羟考酮控释20 mg/片，口服每12 h 1次；加巴喷丁胶囊300 mg/片，口服每12 h 1次。治疗2周后评价疗效。结果：单药组和联合组总有效率分别为70.83%（17/24）、91.67%（22/24），比较差异有统计学意义（P〈0.05）。患者不良反应主要是便秘，恶心呕吐。结论：盐酸羟考酮控释片联合加巴喷丁治疗癌症神经病理性疼痛明显优于单药盐酸羟考酮控释片方案，两种药物联合使用相互取长补短，止痛效果好，安全有效并且不良反应无明显增加，值得进一步深入研究和临床推广使用。     

加巴喷丁减轻骨癌痛大鼠的机械痛敏

目的 观察不同剂量加巴喷丁对胫骨癌痛大鼠机械痛敏的影响.方法 雌性SD大鼠42只,随机分为7组(n=6),即空白对照组(N组)、假手术+生理盐水组(SN组)、假手术+加巴喷丁200 mg ·kg-1·d-1组(SG200组)、骨癌痛+生理盐水组(BN组)、骨癌痛+加巴喷丁50mg·kg-1·d-1组(BG50组)、骨癌痛+加巴喷丁100mg·kg-1·d-1组(BG100组)和骨癌痛+加巴喷丁200mg· kg-1·d-1组(BG200组).从术后第7天起,在保持正常饮水量的前提下,SG200组、BG50组、BG100组和BG200组每天分别按体重将加巴喷丁200mg/kg、50 mg/kg、100 mg/kg、200 mg/kg溶于5 ml生理盐水中饲喂,N组、SN 组和BN组仅给予同等量的生理盐水.分别在术前、术后1,3,5,7d和8,10,12,14d(分别对应为给药后1,3,5,7d)测定右后肢机械缩足阈值(MWT)和自由行走痛行为评分.结果 术后第7天,骨癌痛大鼠MWT [ (3.78 ±0.38)g]和自由行走痛评分[(0.76 ±0.44)分]与空白对照组[(14.50 ±1.38)g,(0.00±0.00)分]和假手术组[(10.21±0.88)g,(0.00±0.00)分]比较,差异具有统计学意义(P＜0.05).在连续应用加巴喷丁的1周中,SN组和SG200组大鼠行为学的差异无统计学意义(P＞0.05); BG50组与BN组比较,MWT无明显差异(P＞0.05),自由行走痛行为评分相对降低,差异有统计学意义(P＜0.05);术后第10天,BG100组[(5.35±0.85)g]和BG200组[(5.71±0.72)g]与BN组[(2.61±0.40)g]和BG50组[(3.28±1.15)g]比较,MWT明显升高,差异有统计学意义(P＜0.05);直到术后14d,差异仍有统计学意义(P＜0.05);从术后第8天起,BG100组和BG200组自由行走痛行为评分较BN组降低,差异有统计学意义(P＜0.05).结论 中到大剂量的加巴喷丁可以缓解骨癌痛大鼠的疼痛症状,但是随着肿瘤骨破坏的加重,加巴喷丁的止痛作用也随之降低.     

加巴喷丁联合硫酸吗啡缓释片治疗中晚期癌症患者放化疗后疼痛的疗效分析

目的观察加巴喷丁联合硫酸吗啡缓释片治疗中晚期癌症患者放化疗后疼痛的效果。方法将61例中晚期癌症患者分成A组20例(硫酸吗啡缓释片组)、B组20例(加巴喷丁组)、C组21例(加巴喷丁联合硫酸吗啡缓释片组),观察3组患者镇痛治疗后的疼痛评分(NRS)、不良反应、睡眠质量(QS)和镇痛药物治疗总费用等。结果 3组患者镇痛治疗后的NRS评分差异有统计学意义(P<0.05);B组与C组患者不良反应的发生率差异无统计学意义(P>0.05),A组与C组患者不良反应的发生率差异有统计学意义(P<0.05);3组患者治疗后的QS比较,差异有统计学意义(P<0.05);镇痛药物治疗总费用比较,B组显著少于A组和C组;C组少于A组(P<0.05)。结论加巴喷丁联合硫酸吗啡缓释片能安全有效地用于中晚期癌症患者放化疗后疼痛的治疗。     

Electro-oxidation and determination of gabapentin at gold electrode

The electrochemical oxidation of gabapentin has been investigated for the first time by cyclic, linear sweep and differential-pulse voltammetry at different pH at gold electrode. Cyclic voltammetric studies were performed in a wide range of sweep rates and various concentrations of gabapentin. The effect of surfactants was studied. The anodic peak was characterized and process was adsorption-controlled. The oxidation peak corresponds to the amine and probable mechanism was proposed. According to the linear relation between the peak current and the gabapentin concentration, differential-pulse voltammetric method for the quantitative determination in pharmaceuticals was developed. The linear response was obtained in the range of 0.3–15 μM with a detection limit of 0.13 μM with good selectivity and sensitivity. The proposed method was successfully applied to gabapentin determination in pharmaceutical samples and for the detection of gabapentin in urine as a real sample.