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PubMed2004

Hot flashes refractory to HRT and SSRI therapy but responsive to gabapentin therapy.

There is a need for alternative therapies for hot flashes, as hormone replacement therapy (HRT) is associated with increased rates of breast cancer and heart disease, and some women fail to respond to HRT. A 32-year-old woman with surgically-induced menopause experienced 20-30 severe hot flashes per day and failed to respond to various formulations of HRT and selective serotonin reuptake inhibitor (SSRI) therapy for 17 years. She markedly responded to gabapentin therapy. Gabapentin, SSRIs, and estrogen may act at different cellular targets in the treatment of hot flashes.

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PubMed2005

Rapid quantification of gabapentin in human plasma by liquid chromatography/tandem mass spectrometry.

A simple, sensitive and rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of gabapentin, a new antiepileptic drug, in human plasma using its structural analogue, 1,1-cyclohexane diacetic acid monoamide (CAM) as internal standard. The method involved a simple protein precipitation by means of acetonitrile followed by a rapid isocratic elution with 10mM ammonium formate buffer/acetonitrile (20/80, v/v, pH 3.0) on Waters Symmetry C(18 reversed phase chromatographic column and analyzed by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 172-->154 and m/z 200-->182 were used to measure the analyte and the IS, respectively. The assay exhibited a linear dynamic range of 40-10000 ng/mL for gabapentin in human plasma. The limit of detection and lower limit of quantification in human plasma were 10 and 40 ng/mL, respectively. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. A run time of 2 min for each sample made it possible to analyze a throughput of more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.

Amines↗
PubMed2003

The clinical use of gabapentin in bipolar spectrum disorders.

BACKGROUND: with increasing awareness of lithium's limitations, several new anticonvulsants had been tested for their mood stabilisation during recent years. Among the innovative third generation mood stabilizing anticonvulsants, gabapentin (GBP) seems to have a broad spectrum of efficacy, although no certain data are available as to its efficacy and use in clinical practice. Accordingly, an extensive review on this subject has been carried out. METHODS: A computer-generated search of the biomedical literature and abstract books of the more important scientific psychiatric congresses until June 2000 was undertaken to identify all pertinent case reports, case series and studies of GBP as monotherapy or adjunctive therapy in mood disorders. We identified 40 open-label studies on the use of GBP in at least 600 patients with bipolar disorder (BP), manic, depressed, or mixed episodes and unipolar depression and four controlled studies. RESULTS: The 40 open-label studies and two of the controlled trials suggested that GBP may have a role as adjunctive agent in the treatment of patients with bipolar disorders particularly when complicated by co-morbid anxiety disorder or substance abuse. GBP is usually very well tolerated and has no pharmacological interference with other mood stabilisers. However, in the other two double-blind studies GBP has not been found to be efficacious in the treatment of refractory mania or refractory bipolar depression. CONCLUSIONS: Although failing to show clear antimanic efficacy in randomized trials, gabapentin still remains a clinically useful agent when it comes to combination treatment in refractory and co-morbid patients.

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PubMed1999

Gabapentin as a promising treatment for antipsychotic-induced movement disorders in schizoaffective and bipolar patients.

Improvement of antipsychotic-induced blepharospasm and involuntary oral-mandibulo movements was observed with the use of the anticonvulsant drug gabapentin among 14 of 16 affectively ill patients who had been exposed to maintenance neuroleptics of the conventional type. In many cases, the movement disorders of these patients had not responded to more standard measures such as clozapine. This finding permits a potential strategy for patients with treatment-emergent tardive dyskinesia, a well-known complication of extended conventional neuroleptic use. Gabapentin, whose mood stabilizing properties have been reported in several clinical reports, represents a more natural treatment in the setting of bipolar spectrum disorders.

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PubMed2000

Gabapentin, an antiepileptic drug, improves memory storage in mice.

Male CF-1 mice were tested 48 h after training in a one-trial step-through inhibitory avoidance task. Immediately post-training i.p. injections of the antiepileptic drug gabapentin (1-aminomethyl cyclohexaneacetic acid) (GBP; 5, 10, 50, and 100 mg/kg) induced a dose-dependent enhancement of retention performance. Gabapentin did not affect response latencies in mice not given the footshock on the training trial, indicating that the actions of GBP on retention were not due to non-specific proactive effects on response latencies. The effects of GBP (10 mg/kg) were time-dependent, and the administration of GBP (10 mg/kg) 30 min before training also enhanced retention performance. However, the administration of GBP (10 mg/kg) 30 min prior to the retention test did not modify retention latencies of mice that had received either saline or GBP (10 mg/kg) immediately after training. Altogether, the results suggest that GBP influences retention by modulating time-dependent processes involved in memory storage, although the mechanism(s) of this action remain to be established.

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PubMed2000

Morphine and gabapentin decrease mechanical hyperalgesia and escape/avoidance behavior in a rat model of neuropathic pain.

A behavioral test paradigm that measures the aversive quality of stimulus-evoked pain in an animal model of neuropathic pain (L5 ligation) was tested for sensitivity to (1) different forces (476 and 202 mN) and frequencies (once every 15 or 30 s) of mechanical stimulation to the hyperalgesic paw and (2) different doses of the common antinociceptive compounds morphine (1 and 10 mg/kg) and gabapentin (30 and 90 mg/kg). Compared to non-ligated controls, the greater force (476 mN) and frequency (every 15 s) of mechanical stimulation of the hyperalgesic paw was associated with the greatest degree of escape/avoidance behavior. There was not a significant degree of escape/avoidance behavior at the lowest force (202 mN) and frequency (every 30 s) of mechanical stimulation. Compared to ligated vehicle treated controls, morphine (1 mg/kg) and gabapentin (90 mg/kg) decreased mechanical hyperalgesia and also attenuated the escape/avoidance behavior. The antinociceptive and antiaversive effects were found at doses that did not produce evidence of decreased motor activity. It is concluded that the behavioral test paradigm used to measure the aversiveness of stimulus-evoked nociceptive behavior is sensitive to different degrees of evoked pain and traditional analgesic compounds.

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PubMed2003

ATP-sensitive potassium channels in rat primary afferent neurons: the effect of neuropathic injury and gabapentin.

ATP-sensitive potassium (K(ATP)) currents were examined in dorsal root ganglion neurons from neuropathic and control rats using whole-cell voltage clamp recordings. K(ATP) channel openers (diazoxide and pinacidil) enhanced, and the blocker glibenclamide inhibited an outward current in control neurons in a manner dependent on the pipette ATP concentration. Analysis of reversal potentials showed that this current is carried by K(+) ions. Outward current in cells from rats with peripheral nerve injury was not sensitive to modulators of K(ATP) channels. Gabapentin, a putative K(ATP) channel opener, had minimal effect on currents in either group of neurons. We conclude that normal primary afferent neurons express K(ATP) channels that conduct current which is eliminated by peripheral nerve injury. Gabapentin does not affect this current significantly.

ATP-Binding Cassette Transporters↗
PubMed2002

Case reports - reversal of sensory deficit associated with pain relief after treatment with gabapentin.

Many patients with neuropathic pain have coexistent sensory deficits. Neuropathic pain may be alleviated by a variety of drugs but sensory deficits are assumed to be permanent. In an audit of the effects of gabapentin therapy on patients with neuropathic pain, monthly detailed sensory examinations were performed during the first three months of treatment. Of five patients with sensory deficits who tolerated gabapentin therapy, three showed marked improvement of their sensory deficits associated with pain alleviation. The cases are presented and possible explanations for the observed sensory improvements are discussed. These findings raised exciting neurophysiological questions in addition to being of potential importance to the clinical problem of neurotrophic tissue injury.

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PubMed2003

Comparative activity of the anti-convulsants oxcarbazepine, carbamazepine, lamotrigine and gabapentin in a model of neuropathic pain in the rat and guinea-pig.

Anti-epileptic drugs (AEDs) are increasingly used for the treatment of neuropathic pain. Oxcarbazepine is a recently introduced AED that is effective in treating epilepsy and has an improved side-effect profile compared to existing therapies. Here we have examined the effect of oxcarbazepine and other AEDs in a model of neuropathic pain in the rat and guinea-pig. Oxcarbazepine and carbamazepine (3-100 mg x kg(-1)) did not affect mechanical hyperalgesia or tactile allodynia induced by partial sciatic nerve ligation in the rat following oral administration. However, in the same model in the guinea-pig, both drugs produced up to 90% reversal of mechanical hyperalgesia with respective D(50) values of 10.7 and 0.8 mg x kg(-1). The active human metabolite of oxcarbazepine, monohydroxy derivative, was similarly active against mechanical hyperalgesia in the guinea-pig but not the rat. Lamotrigine (3-100 mg x kg(-1), p.o.) was effective against mechanical hyperlagesia in both species although it showed greater efficacy and potency in the guinea-pig (D(50) 4.7 mg x kg(-1)) compared to the rat (D(50) 27 mg kg(-1)). Lamotrigine produced slight inhibition of tactile allodynia in the rat only at the highest dose tested of 100 mg x kg(-1). Gabapentin was poorly active against mechanical hyperalgesia in both the rat and guinea-pig following a single oral administration (100 mg x kg(-1)), although upon repeated administration it produced up to 70 and 90% reversal in rat and guinea-pig, respectively. Gabapentin did however produce significant dose-related reversal of tactile allodynia in the rat following a single administration. These data show that oxcarbazepine and other AEDs are effective anti-hyperalgesic or anti-allodynic agents in an animal model of neuropathic pain, and provide further support for their use in the treatment of neuropathic pain in the clinic.

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PubMed1998

Gabapentin induced polyneuropathy.

Gabapentin is an effective option for the treatment of neuropathic pain syndromes because of its efficacy and favorable side-effect profile. A case is presented of a 58 year old man who developed a painful polyneuropathy while being treated with gabapentin.

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PubMed1998

A case of spinal cord injury-related pain with baseline rCBF brain SPECT imaging and beneficial response to gabapentin.

Central pain following spinal cord injury is poorly understood, and is often resistant to conventional pain therapy regimens. We describe an individual with paraplegia who for many years experienced rapidly fluctuating, severe, unilateral pain below the level of his lesion. Prior to the initiation of pharmacological treatment, regional cerebral blood flow (rCBF) was measured during PAIN and NON-PAIN states using single photon emission computed tomography (SPECT). When experiencing pain, the subject had increased anterior cingulate gyrus blood flow, increased thalamic blood flow bilaterally and increased somatosensory cortex blood flow contralaterally but decreased caudate blood flow bilaterally. The subject's subsequent clinical course included a trial of gabapentin which produced a substantial reduction in frequency and average intensity of his episodic pain and which has been maintained for almost 2 years. This case demonstrates the correspondence between rCBF and pain associated with spinal cord injury and also suggests the potential utility of gabapentin for treatment of this central pain state.

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PubMed1998

Sensitive high-performance liquid chromatographic method with fluorometric detection for the simultaneous determination of gabapentin and vigabatrin in serum and urine.

Serum concentrations of the antiepileptic drug gabapentin (GBP) are usually determined by high-performance liquid chromatography (HPLC) using UV photometric detection after pre-column derivatization with 2,4,6-trinitrobenzenesulphonic acid. Vigabatrin levels in serum are determined by HPLC using fluorescence detection. Like vigabatrin (VGB), gabapentin has also a primary amine group that easily reacts with o-phthaldialdehyde reagent and produces a fluorescing substance. By the use of fluorometric detection, GBP can be determined more simply, sensitively and simultaneously with VGB. The day-to-day coefficient of variation for the determination of GBP in a pooled serum was 4.0% (n=17; serum concentration, 13.8 micromol/l) and forVGB was 3.1% (n=21; serum concentration, 26.4 micromol/l). The lower limit of detection is 0.5 micromol/l for both drugs and the method is linear up to 500 micromol/l for GBP and 1300 micromol/l for VGB.

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PubMed2001

Gabapentin for pain control in cancer patients' wound dressing care.

A patient with mycosis fungoides illustrates the problem of pain management during wound care and suggests the utility of a novel treatment, gabapentin. Skin lesions, be they induced through necrosis of tumor, therapy (e.g., radiotherapy), or by pressure ulceration, are often the cause of continuous pain or acute wound dressing pain. Optimizing the analgesic treatment in those patients is thus of major importance. Anti-inflammatory drugs and opioids are the cornerstones in the treatment of cancer pain but are rarely sufficient to control wound pain. Different adjuvant techniques can be used, including topical analgesics, psychological distraction techniques, anxiolytics, and co-analgesics. There is growing evidence that anticonvulsants, and sodium channel blockers in particular, are effective not only in neuropathic but also in inflammatory pain. Gabapentin, a voltage sensitive sodium and calcium channel blocker, was used as a co-analgesic to supplement morphine in this case of cancer wound dressing pain.

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PubMed2000

Gabapentin treatment in a child with delayed-onset hemichorea/hemiballismus.

A 13-year, 6-month-old female was evaluated for subacute onset of left-sided hemichorea/hemiballismus, with an old, right parietal, cortical, and subcortical stroke as the presumed cause. Treatment with gabapentin was initiated, with good results at 6-month follow-up. Discussion of the differential diagnosis and evaluation of delayed-onset movement disorders in children and the mechanism of action of gabapentin is included.

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PubMed2000

Use of gabapentin in the treatment of childhood reflex sympathetic dystrophy.

Reflex sympathetic dystrophy, a painful syndrome involving an extremity after trauma or injury, is increasingly reported in the pediatric population. Although no clear pathophysiologic mechanism for this disorder has been identified, the role of central serotonin activity seems important. Gabapentin, a new antiepileptic medication, has been demonstrated to be effective in adults with reflex sympathetic dystrophy. The first reported case of a child with a diagnosis of reflex sympathetic dystrophy who was treated successfully with gabapentin is presented.

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PubMed1999

Gabapentin as monotherapy in the treatment of acute mania.

Two cases of mania treated with gabapentin, a new anticonvulsant, are presented. After 2 weeks of treatment a moderate improvement of both patients was observed. The antimanic effect of gabapentin awaits confirmation by systematic, well designed studies.

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PubMed1998

Treatment of seizures in acute intermittent porphyria: safety and efficacy of gabapentin.

Treatment of seizures in acute intermittent porphyria represents a therapeutic dilemma. Patients needing chronic therapy often experience acute porphyric attacks due to increased hepatic metabolism induced by the antiepileptic drugs themselves. Gabapentin is a new antiepileptic drug not appreciably metabolized by the liver in humans, and it appears to be safe and effective in the maintenance therapy of epilepsy in these patients. We report a patient affected by partial and generalized seizures in the course of acute intermittent porphyria, who was safely and successfully treated with gabapentin.

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