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PubMed1993

Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy.

Gabapentin is an antiepileptic drug with an unknown mechanism of action apparently dissimilar to that of other antiepileptic agents, and possessing some desirable pharmacokinetic traits. The drug is not protein bound, is not metabolised and does not induce liver enzymes, diminishing the likelihood of drug interactions with other antiepileptic agents and drugs such as oral contraceptives. Although gabapentin is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA), which does not cross the blood-brain barrier, gabapentin penetrates into the CNS and its activity is seemingly distinct from GABA-related effects. Present clinical evaluation is largely restricted to proof of efficacy trials of gabapentin as add-on therapy in patients with partial epilepsy resistant to conventional treatment. Gabapentin (usually 600 to 1800 mg/day) provides notable benefit, reducing seizure frequency by > or = 50% in 18 to 28% of patients with refractory partial seizures, as shown in 3 double-blind, placebo-controlled trials. Overall, seizure frequency decreased by 18 to 32% during 3-month treatment periods. Patients with complex partial seizures, and partial seizures secondarily generalised, are particularly likely to respond to gabapentin. Current experience with the drug in other seizure types, and as monotherapy, is limited. Mild adverse events, commonly somnolence, fatigue, ataxia and dizziness, have been reported in about 75% of gabapentin recipients. While the drug has been well tolerated when administered to a few patients for periods of up to 5 years, its long term tolerability profile has yet to be fully expounded. Thus, with its favourable pharmacokinetic profile, and efficacy in some refractory patients, gabapentin is poised to fill a niche as an adjunct to the treatment of partial epilepsy. Promising results obtained thus far warrant further work to clarify its long term tolerability, its possible efficacy in other seizure types, its position relative to other agents and its use as monotherapy. In the meantime, gabapentin is likely to provide a much-needed option in a therapeutic area requiring complex management.

Acetates↗
PubMed2003

Spinal gabapentin and antinociception: mechanisms of action.

Spinal gabapentin has been known to show the antinociceptive effect. Although several assumptions have been suggested, mechanisms of action of gabapentin have not been clearly established. The present study was undertaken to examine the action mechanisms of gabapentin at the spinal level. Male SD rats were prepared for intrathecal catheterization. The effect of gabapentin was assessed in the formalin test. After pretreatment with many classes of drugs, changes of effect of gabapentin were examined. General behaviors were also observed. Intrathecal gabapentin produced a suppression of the phase 2 flinching, but not phase 1 in the formalin test. The antinociceptive action of intrathecal gabapentin was reversed by intrathecal NMDA, AMPA, D-serine, CGS 15943, atropine, and naloxone. No antagonism was seen following administration of bicuculline, saclofen, prazosin, yohimbine, mecamylamine, L-leucine, dihydroergocristine, or thapsigargin. Taken together, intrathecal gabapentin attenuated only the facilitated state. At the spinal level, NMDA receptor, AMPA receptor, nonstrychnine site of NMDA receptor, adenosine receptor, muscarinic receptor, and opioid receptor may be involved in the antinociception of gabapentin, but GABA receptor, L-amino acid transporter, adrenergic receptor, nicotinic receptor, serotonin receptor, or calcium may not be involved.

Acetates↗
PubMed2001

Gabapentin antinociception in mice with acute herpetic pain induced by herpes simplex virus infection.

The effects of systemic and local injections of gabapentin, a novel anticonvulsant agent, were tested on nociceptive behaviors in mice with acute herpetic pain. Transdermal infection with herpes simplex virus type-1 (HSV-1) produced nociceptive hypersensitivity of the infected hind paw to innocuous (allodynia) and noxious mechanical stimulation (hyperalgesia) with von Frey filaments. Systemic administration of gabapentin (10-100 mg/kg, peroral) produced a dose-dependent inhibition of both allodynia and hyperalgesia; gabapentin (30-300 mg/kg) did not affect locomotor activity. Intrathecal injection of gabapentin (10-100 microg/animal) also attenuated dose dependently both nociceptive hypersensitivities. In contrast, intraplantar, intracisternal, and intracerebroventricular administration of gabapentin (10-100 microg/animal) had no effect on the HSV-1-induced nociceptive hypersensitivities. Pretreatment with naltrexone (1 mg/kg) inhibited antinociceptive effect of morphine (5 mg/kg), but not gabapentin (100 mg/kg). Repeated administration of morphine (5 mg/kg, four times) led to tolerance of antinociceptive action, whereas gabapentin (100 mg/kg, four times) had antinociceptive effect even after the forth administration. The present results suggest that gabapentin is effective in the treatment of acute herpetic pain without apparent adverse effects, and analgesic action of gabapentin is mainly mediated by actions on the spinal cord.

Acetates↗
PubMed2001

Efficacy and safety of gabapentin as an add-on therapy in refractory partial epileptic patients.

The study on the efficacy and safety of gabapentin as an add-on therapy trial was performed in 10 refractory partial seizure cases at Prasat Neurological Institute, Thailand from September 1996 to July 1998. This was an open-labeled titration dose of gabapentin starting at 600 mg/day add-on to the previously prescribed conventional antiepileptic drugs (AEDs). In cases that seizures could not be controlled, gabapentin dose was increased by 300 mg per day every two weeks until the total dose of 3,000 mg or until the side effects became intolerable. The result revealed that gabapentin reduced frequency, duration and severity of seizures and also improved the patients' activities of daily living (ADL) even at the minimum dose of 600 mg. The optimal dose of gabapentin was in the range of 600 to 1,200 mg per day. Seven patients were seizure free at the end of the study. There were some precipitating factors that interfered with the efficacy of gabapentin in some patients such as stress, menstruation, fever, and alcohol intake. Weight gain, somnolence, nystagmus, and dizziness were the major adverse events in these patients, whereas ataxia, tremor, and diplopia were found with gabapentin in a dose higher than 1,800 mg/day. These adverse events were mild and transient. No patients withdrew from the study due to adverse drug reactions. In addition, gabapentin did not alter conventional AED blood level and routine laboratory parameters. In conclusion, gabapentin was effective and well tolerated as an add-on therapy in refractory partial epileptic Thai patients.

Acetates↗
PubMed2003

[Effect of anticonvulsant gabapentin on visceral nociception and its relationship with amino acid neurotransmitters released from spinal cord].

OBJECTIVE: To test whether gabapentin, an anticonvulsant, is able to inhibit responses to peritoneal irritation-induced visceral pain and to examine the effect of gabapentin on spinal cord amino acid release. METHODS: Forty-eight SD rats randomly received intraperitoneal (i.p.) injection of saline or gabapentin (50, 100, or 200 mg.kg-1), and 40 minutes later, 0.6% acetic acid (4 ml.kg-1) was administrated intraperitoneally. The acetic acid-induced writhing assay was used to determine the degree of nociception. The beam balance task was employed to test a possible inhibitory or sedative effect of the central nervous system. Cerebrospinal fluid dialysate was collected by microdialysis from the spinal subarachnoid space in anesthetized rats. Concentrations of amino acids in the dialysate, including glutamate, aspartate, serine, glutamine and glycine, following i.p. injection of acetic acid were evaluated. The effects of pretreatment with saline or gabapentin (100 mg.kg-1 i.p.) on amino acid release were compared. RESULTS: Gabapentin reduced writhing responses in a dose-related fashion. Beam-balance time was significantly shortened after pretreatment with 200 mg.kg-1 of gabapentin. Dialysate concentrations of glutamate, aspartate and serine increased significantly-following i.p. injection of acetic acid, while glutamine and glycine concentrations were not. When compared to saline-treated rats, animals pre-treated with 100 mg.kg-1 of gabapentin showed suppression of the acetic acid-induced increases in glutamate, aspartate and serine concentrations. CONCLUSION: These data demonstrate that gabapentin effectively inhibited acetic acid-induced nociception, and the antinociceptive effect of gabapentin might correlate with the suppression of noxious-evoked release of excitatory amino acids in the spinal cord.

Acetates↗
PubMedDate not supplied

Gabapentin use in a managed medicaid population.

OBJECTIVE: The use of gabapentin, an antiepileptic agent, in a primary care setting was evaluated to determine (a) the conditions being treated, (b) specialties of the prescribers, (c) dose ranges, and (d) the extent of documentation and follow-up. METHODS: A retrospective review of both claims data and patient charts was performed by a clinical pharmacist. Patients were identified from CareOregon and Oregon Medicaid fee-for-service drug claim databases. All patients were recipients of the Oregon Medicaid program known as the Oregon Health Plan (OHP) and were enrolled members of CareOregon, a contracted OHP managed care organization that primarily serves Medicaid recipients. All patients received care at one of four Oregon Health and Science University primary care clinics. RESULTS: Of the 105 patients studied, 95% received gabapentin for off-label diagnoses. Chronic pain and mental disorders were the diagnoses associated with the majority of prescriptions for gabapentin. Dose and dose intervals varied greatly. Very few patients (12%) had a documented efficacious response to gabapentin therapy. Of the patients started on gabapentin, 40% of patients had no documented follow-up. CONCLUSIONS: Almost all patients in this sample from the Medicaid managed population received gabapentin for off-label indications. Evidence from clinical trials does not support the use of gabapentin for many of the conditions treated with gabapentin in this study. Most patients did not appear to benefit from gabapentin therapy.

Journal Article↗
PubMed2005

Gabapentin for acute and chronic pain.

BACKGROUND: Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning. OBJECTIVES: To evaluate the analgesic effectiveness and adverse effects of gabapentin for pain management in clinical practice. SEARCH STRATEGY: Randomised trials of gabapentin in acute, chronic or cancer pain were identified by MEDLINE (1966-Nov 2004), EMBASE (1994-Nov 2004), SIGLE (1980-Jan 2004) and the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 4, 2004). Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators. Date of most recent search: January 2004. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of gabapentin in patients, with subjective pain assessment as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Numbers-needed-to-treat (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal. MAIN RESULTS: Fourteen reports describing 15 studies of gabapentin were considered eligible (1468 participants). One was a study of acute pain. The remainder included the following conditions: post-herpetic neuralgia (two studies), diabetic neuropathy (seven studies), a cancer related neuropathic pain (one study) phantom limb pain (one study), Guillain Barré syndrome (one study) , spinal chord injury pain (one study) and various neuropathic pains (one study). The study in acute post-operative pain (70 participants) showed no benefit for gabapentin compared to placebo for pain at rest. In chronic pain, the NNT for improvement in all trials with evaluable data is 4.3 (95%CI 3.5-5.7). Forty two percent of participants improved on gabapentin compared to 19% on placebo. The number needed to harm(NNH) for adverse events leading to withdrawal from a trial was not significant. Fourteen percent of participants withdrew from active arms compared to 10% in placebo arms. The NNH for minor harm was 3.7 (95% CI 2.4 to 5.4). The NNT for effective pain relief in diabetic neuropathy was 2.9 (95% CI 2.2 to 4.3) and for post herpetic neuralgia 3.9 (95% CI 3 to 5.7). AUTHORS' CONCLUSIONS: There is evidence to show that gabapentin is effective in neuropathic pain. There is limited evidence to show that gabapentin is ineffective in acute pain.

Acute Disease↗
PubMed2006

Preemptive gabapentin reduces postoperative pain and opioid demand following thyroid surgery.

PURPOSE: Gabapentin is reported to possess antihyperalgesic and antiallodynia properties. Recently, reports have indicated that gabapentin may have a place in the treatment of postoperative pain. In this study, we sought to determine whether preemptive use of gabapentin reduced postoperative pain and morphine demand following thyroidectomy. METHODS: In this prospective, randomized, double-blind clinical trial, we gave gabapentin 1200 mg or placebo two hours prior to induction of anesthesia to patients undergoing elective thyroidectomy. Post-thyroidectomy pain was assessed on a visual analogue scale at rest and during swallowing in the first 24 hr postoperatively. All patients received morphine 3 mg iv every five minutes until visual analogue scale scores were 4 or less at rest, and 6 or less with swallowing. Total morphine consumption for each patient was recorded from zero to 24 hr postoperatively. RESULTS: Thirty-seven patients in the gabapentin group and 35 patients in the placebo group completed the study. Overall, pain scores at rest and during swallowing in the gabapentin group were significantly lower when compared with the placebo group. Total postoperative morphine consumption in the gabapentin group was 15.2 +/- 7.6 mg (mean +/- SD) vs 29.5 +/- 9.9 mg in the placebo group (P < 0.001). No significant differences in side effects were observed between groups. CONCLUSIONS: Preoperative gabapentin decreased pain scores and postoperative morphine consumption in patients following thyroid surgery.

Amines↗
PubMed2006

Venlafaxine compromises the antinociceptive actions of gabapentin in rat models of neuropathic and persistent pain.

RATIONALE: Neuropathic pain is associated with a number of disease states of diverse aetiology that can share common pathophysiological mechanisms. Antiepileptic drugs modulate ion channel function and antidepressants increase extracellular monoamine levels, and both drug classes variously attenuate signs and symptoms of neuropathic pain. Thus, coadministration of the antiepileptic gabapentin and the antidepressant venlafaxine may provide superior pain relief to administration of either drug alone. OBJECTIVES: To systematically establish the pain relieving efficacies of venlafaxine and gabapentin alone and in combination. MATERIALS AND METHODS: Gabapentin (50 and 100 mg/kg, s.c.) and venlafaxine (10, 25, 50 mg/kg, s.c.) were tested alone or in combination in the rat spared nerve injury (SNI) model of neuropathic pain and the rat formalin test of persistent pain. Diuresis was measured in a separate experiment after administration of venlafaxine. RESULTS: Hindpaw mechanical allodynia was dose-dependently reversed by gabapentin (50 and 100 mg/kg, s.c.), whereas venlafaxine was ineffective (10 and 50 mg/kg, s.c.). Both gabapentin and venlafaxine also attenuated hindpaw mechanical hyperalgesia. Surprisingly, coadministration of venlafaxine (50 mg/kg) significantly lowered the antiallodynic effect of both doses of gabapentin by up to 60% in spared-nerve-injury rats and a negative antinociceptive interaction between gabapentin and venlafaxine was also observed in the rat formalin test. We demonstrated that venlafaxine administration was associated with a dose-dependent increase in urine output over the time course of the nociceptive experiments. CONCLUSION: Venlafaxine compromises the antiallodynic effects of coadministered gabapentin most probably as consequence-increased diuresis.

Amines↗
PubMed2001

Effect of gabapentin-like compounds on development and maintenance of morphine-induced conditioned place preference.

RATIONALE: Psychological dependence to the opioid analgesic morphine is attributable to the rewarding properties of the drug, and its evolution can be divided into two distinct phases: development and maintenance. Both phases can be studied using conditioned place preference (CPP). OBJECTIVES: To determine whether the two phases can be influenced by pre-treatment with gabapentin-like compounds. METHODS: CPP to morphine was used to demonstrate the rewarding properties of morphine in the presence or absence of gabapentin-like compounds. In-vivo microdialysis in the nucleus accumbens was used to determine the effects of gabapentin or pregabalin on morphine-induced dopamine release. RESULTS: Pretreatment with either gabapentin (10-100 mg/kg p.o.) or pregabalin (3-30 mg/kg p.o.) attenuated CPP induced by a submaximal dose of morphine (0.75 mg/kg). Neither gabapentin nor pregabalin had any effect alone in the CPP test. Both gabapentin-like compounds blocked the effect of morphine (0.75 mg/kg s.c.) to increase the release of dopamine in the nucleus accumbens. Studies of the maintenance of CPP to morphine showed CPP was maintained for at least 4 days after the initial test. In a second experiment, it was found that pregabalin (injected once, 24 h after CPP had been demonstrated) was able to reverse morphine-induced CPP. CONCLUSIONS: Neither gabapentin nor pregabalin induced CPP, but both compounds blocked the development of CPP to morphine and also blocked morphine's effects on dopamine release. Furthermore, pregabalin blocked the maintenance of morphine-induced CPP. It is concluded that gabapentin-like compounds, which have no intrinsic rewarding properties, may have some therapeutic use in the treatment of opioid dependence.

Acetates↗
PubMed2005

Chronic pelvic pain treated with gabapentin and amitriptyline: a randomized controlled pilot study.

BACKGROUND: The aim of this study was to compare the efficacy and side effects of gabapentin, amitriptyline, and their combination in women with chronic pelvic pain. METHODS: In this open-label, prospective, randomized trial, 56 women with chronic pelvic pain were investigated with a two-year follow-up at the Vienna Medical University Hospital. If pain intensity assessed by a visual analog scale (VAS) was 5 or more (0, no pain; 10, maximal pain), despite analgesic therapy using the nonopioid drug metamizol together with weak opioids, patients were randomized to receive gabapentin (n = 20), amitriptyline (n = 20), or a combination of both drugs (n = 16). Doses of gabapentin and amitriptyline were increased to maximum daily doses of 3600 mg and 150 mg, respectively, until sufficient pain relief or the occurrence of side effects. VAS and side effects were evaluated before treatment and at 1, 3, 6, 12 and 24 months afterwards. RESULTS: All patients experienced significant pain relief during the observation period. However, after 6, 12 and 24 months, pain relief was significantly better in patients receiving gabapentin either alone or in combination with amitriptyline than in patients receiving monotherapy with amitriptyline (gabapentin: 0 months, 7.7 +/- 1.5; 6 months, 1.6 +/- 0.9; 12 months, 1.5 +/- 0.9; 24 months, 1.9 +/- 0.9; amitriptyline: 0 months, 7.3 +/- 1.5; 6 months, 2.2 +/- 1.6; 12 months, 2.2 +/- 1.6; 24 months; 3.4 +/- 0.9; amitriptyline-gabapentin: 0 months, 7.6 +/- 0.8; 6 months, 1.3 +/- 0.9; 12 months, 1.7 +/- 1.0; 24 months, 2.3 +/- 0.9). Side effects were lower in the gabapentin group than in the two other groups, the difference reaching statistical significance after three months (P < 0.05). CONCLUSION: Gabapentin alone or in combination with amitriptyline is better than amitriptyline alone in the treatment of female chronic pelvic pain.

Adult↗
PubMedDate not supplied

Efficacy and tolerability of gabapentin in clinical practice.

The efficacy and tolerability of gabapentin therapy for seizures in patients in clinical practice were retrospectively evaluated. Demographics, seizure type and history, prior anticonvulsant therapy, concomitant anticonvulsant medications, gabapentin dosing, side effects, seizure response, and tolerability data were obtained from 100 consecutive clinical practice patients (47 men and 53 women) treated with gabapentin. All patients had been previously treated with a mean of 2.9 anticonvulsant drugs and were currently taking a mean of 1.75 anticonvulsant drugs. Seventy-two patients experienced a greater than 50% reduction in seizures, and 23 of these patients experienced a greater than 75% reduction; 57 patients continued gabapentin treatment, 5 of whom remain seizure free and side effect free with gabapentin monotherapy. Of the 42 patients discontinuing treatment, 17 had no seizure reduction, 17 had side effects, and 8 had both. One additional patient died. The mean daily dosage for all 100 patients was 2107 mg, and the mean daily dosage for patients who continued gabapentin treatment was 2270 mg. No linear relationship was found between dosage and patient weight. Fifty-two patients had the dosage of at least 1 concomitant anticonvulsant medication reduced, 31 had at least 1 concomitant anticonvulsant medication removed from the regimen, and 9 required a dosage increase of at least 1 anticonvulsant medication. Twenty patients experienced fatigue, which was usually transient after treatment initiation; in 13 patients fatigue was associated with carbamazepine therapy. In addition, 7 patients experienced ataxia (6 of whom were taking concomitant carbamazepine), and 2 experienced weight gain. Patients experiencing side effects resulting in discontinuation were taking a mean daily dose of gabapentin of 1182 mg. The maximum effective and tolerable daily dosage under clinical practice conditions appears to exceed dosages established in clinical trials. The results of our study suggest broader treatment parameters for gabapentin than initially determined in the more restrictive clinical trials conducted during the drug's development.

Acetates↗
PubMed1993

Characterisation of [3H]gabapentin binding to a novel site in rat brain: homogenate binding studies.

The binding characteristics of [3H]gabapentin, the radiolabelled analogue of the novel anticonvulsant gabapentin (1-(aminomethyl)cyclohexaneacetic acid) were studied using purified synaptic plasma membranes prepared from rat cerebral cortex. In 10 mM HEPES buffer [3H]gabapentin bound to a single population of sites with high affinity (KD = 38 +/- 2.8 nM) with a maximum binding capacity of 4.6 +/- 0.4 pmol/mg protein, reaching equilibrium after 30 min at 20 degrees C. This novel site was unique to the central nervous system with little or no specific [3H]gabapentin being measurable in a range of peripheral tissues. Binding was potently inhibited by a range of gabapentin analogues and 3-alkyl substituted gamma-aminobutyric acid (GABA) derivates although GABA itself and the selective GABAB receptor ligand baclofen, were only weakly active. Gabapentin itself (IC50 = 80 nM) and 3-isobutyl GABA (IC50 = 80 nM) which also has anticonvulsant properties, showed the highest affinity for the binding site. Of a wide range of other pharmacologically active compounds only the polyamines spermine and spermidine influenced [3H]gabapentin binding, with both compounds producing a maximum of 50% inhibition of specific binding. Magnesium ions produced a similar pattern of inhibition but the effect of the polyamines and magnesium ions were not additive. The data provide evidence for the existence in brain of a novel binding site that may mediate the anticonvulsant effects of gabapentin and other potential anticonvulsant compounds.

Acetates↗
PubMed2005

A randomized placebo-controlled trial of gabapentin for cocaine dependence.

BACKGROUND: In laboratory animals, augmentation of GABA neurotransmission results in inhibition of cocaine self-administration and inhibition of reinstatement to cocaine-seeking behaviors. If parallel effects were observed in humans, GABA-ergic medication should be effective both in the abstinence-induction as well as in the relapse-prevention phase of cocaine dependence treatment. Gabapentin is an anticonvulsant medication that increases human brain GABA levels. We evaluated the safety and efficacy of gabapentin combined with relapse-prevention therapy in the treatment of cocaine-dependent individuals. DESIGN: The study involved 129 individuals with cocaine dependence. Of the 99 participants, who were randomized into a double-blind trial 88% were males, 66% were minorities and with an average age of 39 years (range 22-58 years). After 2 weeks of placebo lead-in, participants were randomized to receive either gabapentin 3200 mg (1600 mg bid) or placebo for 12 weeks, followed by 2 weeks of placebo lead-out. Prior to randomization, participants were stratified into four groups based on the principal route of cocaine use (smokers versus intranasal users) and the level of cocaine use during the 2 weeks of lead-in (high level versus low level). Throughout the 16 weeks study, participants received weekly individual relapse-prevention therapy. The outcome measures included: days of cocaine use and a binary indicator of abstinence based on urine toxicology test, self-reported cocaine craving and retention in treatment. RESULTS: Forty-nine percent of randomized patients completed 12 weeks of the trial. Retention did not differ by treatment group but cocaine-smokers dropped out of treatment at a significantly faster rate than intranasal users. For the entire sample, odds of cocaine use over the course of the study did not differ between gabapentin- and placebo-treated individuals. There was a significant difference in the odds of cocaine use between high and low-use groups, with the odds in high-use groups decreasing over time and odds in the low-use groups gradually increasing over the course of the study, such that by the end of the study low and high users were similarly likely to use cocaine. In the low-use group, there was a non-significant trend suggesting that gabapentin-treated subjects had more favorable outcome compared to placebo-treated individuals. There was no treatment effect on abstinence rates, craving or other substance use. Gabapentin at 3200 mg/day was very well tolerated in this group of cocaine-dependent participants. CONCLUSIONS: When combined with weekly individual relapse-prevention therapy, gabapentin 1600 mg bid was no more effective than placebo in the treatment of cocaine dependence. When reviewed in conjunction with other published studies, gabapentin and other GABA enhancing anticonvulsant medications may deserve further study as relapse-preventive agents in cocaine-dependent individuals who achieve abstinence early in treatment.

Adult↗
PubMed2006

Clinical efficacy of gabapentin versus tiagabine for reducing cocaine use among cocaine dependent methadone-treated patients.

BACKGROUND: GABAergic medications appear to reduce the reinforcing effects of cocaine by attenuating cocaine-induced dopamine release. This study evaluated gabapentin and tiagabine compared to placebo in reducing cocaine taking behavior. METHODS: A total of 76 treatment seeking, cocaine dependent, methadone-treated, predominately Caucasian male subjects were randomly assigned to tiagabine 24 mg/day (N=25), gabapentin 2400 mg/day (N=26) or placebo (N=25) in a 10-week double-blind placebo-controlled trial. Study medications were slowly increased to their full dosages by the end of week 5 and maintained through week 10. The primary outcome measure was thrice-weekly drug free urine samples. RESULTS: Treatment retention was significantly less for the gabapentin group relative to the other groups (log rank=5.29, d.f.=1, p=0.02). The proportion of cocaine-free urine samples during weeks 6-10 was significantly larger in the tiagabine treated group (p<0.05). The longitudinal data showed significant change in thrice-weekly cocaine free urines that reached a greater abstinent rate for the tiagabine treated group (22%) compared to gabapentin (5%) or placebo (13%) treated groups. Mixed-effects ordinal regression models showed a significant tiagabine by time interaction compared to gabapentin (Z=2.48, d.f.=1, p=0.01) and placebo (Z=3.90, d.f.=1, p=0.0001). The gabapentin group did not differ from placebo. CONCLUSION: Gabapentin showed poor treatment retention and ineffectiveness in reducing cocaine use. Tiagabine significantly reduced cocaine taking behavior compared to placebo or gabapentin among methadone-stabilized cocaine abusers.

Adult↗
PubMed2006

Multiple dose gabapentin attenuates cutaneous pain and central sensitisation but not muscle pain in healthy volunteers.

Various muscle pains constitute a large clinical problem, both for patients and clinicians. Gabapentin is an established therapy in neuropathic pain and reduces cutaneous pain in healthy volunteers. Gabapentin in combination with other analgesics reduces post-operative pain. No data exist on the effect of gabapentin on muscle pain. This study investigates the effect of gabapentin on muscle and cutaneous pain in healthy volunteers. Sixteen healthy volunteers, 8 male/8 female, were included in this double-blind three-session crossover study comparing the effects of 0, 1200, 1800 and 2600 mg (pre-treatment, titrated over 4 doses) gabapentin and placebo. Muscle pain was induced by infusing 0.5 ml of hypertonic saline into the anterior tibial muscle. Simultaneously, subjects graded pain on a computerized visual analog scale (VAS, 0-10). Total (AUC, VAS*duration in s) and maximal pain (VAS(max)) were assessed. Areas of local and referred pain were measured. Further, continuous intracutaneous electrical stimulation was applied to the forearm. Current was increased until pain intensity 5/10 or until subjects reached a cut-off of 70 mA. Spontaneous pain (VAS 0-10), areas of secondary hyperalgesia to pinprick (cm2) and mechanical pain threshold (g) within this area were assessed. Gabapentin pre-treatment reduced sensitivity to electrical induction of skin pain by 14%, p=0.016. Secondary hyperalgesia was induced, but areas were reduced after pre-treatment, p<0.05. Mechanical pain thresholds were unaffected. Pain induced by intramuscular infusion of hypertonic saline was not affected by gabapentin. In conclusion, single or repeated dosing of gabapentin reduced cutaneous but not muscle pain in healthy volunteers.

Adult↗
PubMed2006

Analgesic action of gabapentin on chronic pain in the masticatory muscles: a randomized controlled trial.

Chronic masticatory myalgia (CMM) can be defined as constant pain in the masticatory muscles for more than 6 months and is influenced by the central nervous system. The antiepileptic agent gabapentin acts centrally and is used for managing different types of chronic pain conditions. The objective of this study was to evaluate the analgesic action of gabapentin on CMM. In this 12-week randomized controlled clinical trial 50 patients were randomly allocated into two study groups: 25 received gabapentin and 25 received placebo. The outcome measures utilized were pain reported on a VAS (VAS-pain), Palpation Index (PI) and impact of CMM on daily functioning reported on a VAS (VAS-function). Thirty-six patients completed the study. Gabapentin showed to be clinically and statistically superior to placebo in reducing pain reported by patients (gabapentin=51.04%; placebo=24.30%; P=0.037), masticatory muscle hyperalgesia (gabapentin=67.03%; placebo=14.37%; P=0.001) and impact of CMM on daily functioning (gabapentin=57.70%; placebo=16.92%; P=0.022). It can be concluded from this study that gabapentin is effective for the management of CMM.

Adolescent↗
PubMed1996

The anticonvulsant gabapentin decreases firing rates of substantia nigra pars reticulata neurons.

Gabapentin is a novel anti-epileptic drug which enhances GABA (gamma-aminobutyric acid) turnover in certain brain regions, including substantia nigra. However, the functional consequences of GABA turnover increases in response to gabapentin and their potential involvement in the anticonvulsant action of this drug are not known. In the present study, we examined the effects of gabapentin on the extracellular, single unit activity of nondopaminergic (presumably GABAergic) neurons of the substantia nigra pars reticulata in rats. During the recordings, the animals were infused with the narcotic opioid analgesic fentanyl, associated with a skeletal muscle relaxant and artificial ventilation. The spontaneous firing of substantia nigra pars reticulata neurons was determined up to about 2 h after i.v. or i.p. administration of gabapentin at doses of 15-30 mg/kg. After both routes of administration, gabapentin markedly reduced neuronal firing when administered at a dose of 20-30 mg/kg, while 15 mg/kg were ineffective in this regard. The suppressive effect of gabapentin was rapid in onset (2 min after i.v. and about 20 min after i.p. injection), reached peak values of about 70% below predrug baseline after about 45-60 min, and remained at this level for at least 2 h. Vehicle administration had no effect on substantia nigra pars reticulata neurons. The ability of gabapentin to alter substantia nigra pars reticulata firing does correlate with its known ability to increase nigral GABA turnover. Since a substantial body of evidence suggests that the substantia nigra pars reticulata is a critical site at which decrease of neuronal firing by potentiation of GABAergic influences results in protection against various seizure types, the suppressive effect of gabapentin on substantia nigra pars reticulata activity may contribute to the anticonvulsant action of this drug.

Acetates↗