Cytokine inflammatory threat, but not LPS one, shortens GABAergic synaptic currents in the mouse spinal cord organotypic cultures.

BACKGROUND: Synaptic dysfunction, named synaptopathy, due to inflammatory status of the central nervous system (CNS) is a recognized factor potentially underlying both motor and cognitive dysfunctions in neurodegenerative diseases. To gain knowledge on the mechanistic interplay between local inflammation and synapse changes, we compared two diverse inflammatory paradigms, a cytokine cocktail (CKs; IL-1ß, TNF-α, and GM-CSF) and LPS, and their ability to tune GABAergic current duration in spinal cord cultured circuits. METHODS: We exploit spinal organotypic cultures, single-cell electrophysiology, immunocytochemistry, and confocal microscopy to explore synaptic currents and resident neuroglia reactivity upon CK or LPS incubation. RESULTS: Local inflammation in slice cultures induced by CK or LPS stimulations boosts network activity; however, only CKs specifically reduced GABAergic current duration. We pharmacologically investigated the contribution of GABAAR α-subunits and suggested that a switch of GABAAR α1-subunit might have induced faster GABAAR decay time, weakening the inhibitory transmission. CONCLUSIONS: Lower GABAergic current duration could contribute to providing an aberrant excitatory transmission critical for pre-motor circuit tasks and represent a specific feature of a CK cocktail able to mimic an inflammatory reaction that spreads in the CNS. Our results describe a selective mechanism that could be triggered during specific inflammatory stress.

Bioequivalence of two formulations of pregabalin 150-mg capsules under fasting conditions in healthy male subjects
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BACKGROUND: Pregabalin binds to the α2δ auxiliary subunit of voltage-gated calcium channels, which are widely distributed throughout the central and peripheral nervous systems and modulate calcium-dependent neurotransmitter release. Pregabalin is indicated for the treatment of peripheral and central neuropathic pain, partial seizures with or without secondary generalization, and treatment of generalized anxiety disorder (GAD). OBJECTIVE: The purpose of this study was to assess the bioequivalence of two different formulations of pregabalin 150-mg capsules in healthy Korean male subjects under fasting conditions. METHODS: This bioequivalence study was based on an open-label, single-dose, randomized, 2-period, 2-sequence crossover design with a washout period of 7 days. Blood samples for pharmacokinetic (PK) evaluation were collected up to 24 hours postdose. Plasma concentrations of pregabalin were determined using a validated LC-MS/MS method. PK parameters were determined using noncompartmental analysis. Bioequivalence was assumed if the 90% confidence intervals (CIs) for the test/reference ratios of log-transformed Cmax and AUClast values met the bioequivalence criteria specified by Korean regulatory guidelines (90% CI 0.8 - 1.25). RESULTS: The extent of exposure in terms of AUClast amounted to 26,018.3 - 3,580.8 µg×h/L for the test formulation and 25,680.2 ± 3,083.6 µg×h/L for the reference formulation. Cmax reached values of 4,782.7 ± 1,124.2 µg/L and 4,654.0 ± 911.4 µg/L for the test product and reference product, respectively. The geometric mean ratio and 90% CIs of the test product to the reference product were 1.0132 (0.9862 - 1.0351) for AUClast and 1.0153 (0.9351 - 1.1044) for Cmax, which were well within the range necessary to establish bioequivalence (90% CI 0.8 - 1.25). CONCLUSIONS: The bioequivalence between test and reference formulations under fasting conditions was confirmed both in terms of the rate and extent of absorption.
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Dolor miofascial en el territorio craneocervical: Una revisión de la patología y su relación con polimorfismos genéticos del sistema GABAérgico / Myofascial Pain in the craneocervical territory: A review of the pathology and its relationship with the GABAergic system genetic polymorphisms

El dolor miofascial es una patología muscular regional no inflamatoria caracterizada por la presencia de una zona hiperirritable de tejido muscular que se encuentra en una banda tensa, denominado punto gatillo. En la región orofacial pertenece a un conglomerado de patologías denominadas trastornos temporomandibulares, correspondiendo al de mayor prevalencia. Las manifestaciones clínicas van desde dolor local, tensión muscular y disfunción estructural hasta dolor referido, fenómenos autonómicos e hiperexcitabilidad en el sistema nervioso central. Durante las últimas décadas se han asociado variantes genéticas con diferentes expresiones en patologías dolorosas, algunas de las cuales se encuentran en el sistema GABAérgico. En el presente artículo se realiza una revisión del dolor miofascial como patología y su relación con estos polimorfismos genéticos (AU)

Myofascial pain is noninflammatory regional muscular disorder characterized by the presence of a muscle tissue area hyperirritable located on a taut band, called trigger point. In the orofacial region myofascial pain belongs to a cluster of diseases called temporomandibular disorder. Within these pathologies, it is to the most prevalent of its, clinical manifestations include local pain, muscle tension, structural dysfunction, referred pain, autonomic phenomena and hyperexcitability in the central nervous system. During the last decades have been associated genetic variants to painful pathologies, some of which are in the GABAergic system. This article performs a review of myofascial pain as pathology and its relation to genetic polymorphisms in GABAergic system (AU)

EEG-ß/γ spectral power elevation in rat: a translatable biomarker elicited by GABA(Aα2/3)-positive allosteric modulators at nonsedating anxiolytic doses.

Benzodiazepine drugs, through interaction with GABA(Aα1), GABA(Aα2,3), and GABA(Aα5) subunits, modulate cortical network oscillations, as reflected by a complex signature in the EEG power spectrum. Recent drug discovery efforts have developed GABA(Aα2,3)-subunit-selective partial modulators in an effort to dissociate the side effect liabilities from the efficacy imparted by benzodiazepines. Here, we evaluated rat EEG and behavioral end points during dosing of nine chemically distinct compounds that we confirmed statistically to selectively to enhance GABA(Aα2,3)-mediated vs. GABA(Aα1) or GABA(Aα5) currents in voltage clamped oocytes transfected with those GABA(A) subunits. These compounds were shown with in vivo receptor occupancy techniques to competitively displace [(3)H]flumazenil in multiple brain regions following peripheral administration at increasing doses. Over the same dose range, the compounds all produced dose-dependent EEG spectral power increases in the ß- and and γ-bands. Finally, the dose range that increased γ-power coincided with that eliciting punished over unpunished responding in a behavioral conflict model of anxiety, indicative of anxiolysis without sedation. EEG γ-band power increases showed a significant positive correlation to in vitro GABA(Aα2,3) modulatory intrinsic activity across the compound set, further supporting a hypothesis that this EEG signature was linked specifically to pharmacological modulation of GABA(Aα2,3) signaling. These findings encourage further evaluation of this EEG signature as a noninvasive clinical translational biomarker that could ultimately facilitate development of GABA(Aα2,3)-subtype-selective drugs for anxiety and potentially other indications.

Interaction of valproic acid and the antidepressant drugs doxepin and venlafaxine: analysis of therapeutic drug monitoring data under naturalistic conditions.

Valproic acid and the antidepressants doxepin and venlafaxine are frequently used psychotropic drugs. In the literature, an influence of valproic acid on serum levels of antidepressants has been described, although studies have focused on amitriptyline. The authors assessed their therapeutic drug monitoring (TDM) database for patients receiving a combination of doxepin or venlafaxine and valproic acid and compared these samples with matched controls without valproic acid comedication in terms of the serum concentration of antidepressants. The mean dose-corrected serum concentration of doxepin+N-doxepin in 16 patients who received valproic acid comedication was higher (2.171±1.482 ng/ml/mg) than that in the matched controls (0.971±0.857 ng/ml/mg, P<0.003). We also found a significant correlation between valproic acid serum level and dose-corrected doxepin+N-doxepin serum level (Spearman's ρ r=0.602, P<0.014). The mean dose-corrected serum level of venlafaxine+O-desmethylvenlafaxine in 41 patients who received valproic acid comedication did not differ significantly from that of the matched controls (P<0.089), but there was a significant difference between both groups in the dose-corrected serum level of O-desmethylvenlafaxine (1.403±0.665 vs. 1.102±0.444, P<0.017). As a consequence, if a combination of valproic acid with doxepin or venlafaxine is administered, cautious dosing is advisable and TDM should be performed.

Study of the absolute bioavailability of citrocard, a new GABA derivative.

The main pharmacokinetic parameters attest to short elimination half-life and mean retention time of a single citrocard molecule. The average rate of plasma concentration decrease of the compound determined small area under the pharmacokinetic curve. Steady-state distribution volume was low and only slightly surpassed the volume of extracellular body fluids in rat, which indicated moderate capacity of citrocard to distribution and accumulation in the tissues, which is seen from low systemic clearance (Cl) despite the quick elimination of the compound. Absolute bioavailability was 64%.

Phenazepam: the drug that came in from the cold.

In the past few years there has been concern in Western Europe and in the US about the rise in abuse of phenazepam, a benzodiazepine that was originally developed in the USSR in the mid- to late 1970s.(1-4) Although phenazepam is one of the most widely prescribed benzodiazepines in Russia and other commonwealth of independent state (CIS) countries, it has not been licensed elsewhere in the world. Due to very limited licensed geographical distribution, there is very little peer-reviewed literature that is not written in Russian. In this article, we review the current state of what is currently known about phenazepam. This information on phenazepam and how it can be detected in biological specimens should assist the forensic community in identifying phenazepam in routine toxicology screening and interpreting any phenazepam concentrations that are obtained.

A 12-month randomized, open-label study of the metabolic effects of olanzapine and risperidone in psychotic patients: influence of valproic acid augmentation.

OBJECTIVE: Longitudinal data comparing the metabolic effects of olanzapine and risperidone with or without valproic acid supplementation in schizophrenic and bipolar patients are lacking. METHOD: This study compares the metabolic effects of olanzapine and risperidone in a prospective, randomized, open-label trial in 160 patients with DSM-IV-TR schizophrenia, schizoaffective disorder, or bipolar disorder after 1, 3, 6, and 12 months' treatment. The study was conducted between 2000 and 2006. The primary analysis compared all patients randomized to olanzapine or risperidone; the primary outcome measure was changes in triglycerides (TG), and TG/high density lipoprotein cholesterol (HDL-C) ratio, a risk factor for ischemic cardiovascular disease. Secondary analyses included the effect of concomitant valproic acid. RESULTS: Significantly greater increases in weight (F(4,434) = 4.7), body mass index (BMI) (F(4,424) = 5.1), glycosylated hemoglobin (HgbA1c) (F(4,427) = 4.3), total cholesterol (F(4,429) = 4.4), TG (F(4,426) = 5.9), and TG/HDL-C ratio (F(4,426) = 4.3) (P < .005 for all drug × time interaction effects) were observed at all but the initial time points in the olanzapine- compared to the risperidone patients. Olanzapine/+valproic acid produced significantly greater increases in HgbA1c, BMI, weight, TG, and TG/HDL-C than olanzapine/-valproic acid at 3 and 6 months, while risperidone/+valproic acid produced significantly smaller increases in HgbA1c, BMI, and weight at 1, 3, and 6 months than risperidone/-valproic acid. The olanzapine/+valproic acid group had significantly greater BMI, and weight at 1, 3, and 6 months, and greater HgbA1c at 3 and 6 months, compared with the risperidone/+valproic acid group. There were too few patients treated with mood stabilizers other than valproic acid to analyze effects of any other mood stabilizer separately. Metabolic effects did not differ significantly by diagnostic category (schizophrenia/schizoaffective disorder vs bipolar disorder). CONCLUSION: Further study of the metabolic effects of adjunctive valproic acid is indicated, as valproic acid may produce markedly different metabolic effects when combined with various antipsychotic drugs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00179062.

Effects of benzodiazepine treatment on cortical GABA(A) and muscarinic receptors: studies in schizophrenia and rats.

Changes in cortical γ-aminobutyric acid A (GABA(A)) receptors and muscarinic receptors have been reported in schizophrenia, a disorder treated with antipsychotic drugs and benzodiazepines. As there is a reported functional relationship between the GABAergic and cholinergic systems in the human central nervous system we have investigated whether there are changes in the GABA(A) and muscarinic receptors in the cortex of subjects from APD-treated subjects with schizophrenia and whether changes were different in subjects who had also received benzodiazepine treatment. We failed to show any strong correlations between changes in GABA(A) and muscarinic receptors in the CNS of subjects with schizophrenia. We showed that subjects with schizophrenia treated with benzodiazepines had lower levels of muscarinic receptors; which was not the case in rats treated with APDs, benzodiazepines or a combination of both drugs. Further, the benzodiazepine binding site, but not the muscimol binding site, was decreased in the parietal cortex of subjects with schizophrenia independent of benzodiazepine status at death. These data would therefore support our previously stated hypotheses that changes in the cortical cholinergic and GABAergic systems are involved in the pathophysiology of schizophrenia.

Pregabalin reduces sleep disturbance in patientswith generalized anxiety disorder via bothdirect and indirect mechanisms

Background and Objectives: To characterize the impact of pregabalin onsleep in patients with generalized anxiety disorder (GAD) and to determine whether the impactis a direct or an indirect effect, mediated through the reduction of anxiety symptoms.Methods: A post-hoc analysis of data from a randomized, double-blind, placebo- and active-controlled study in patients with GAD was conducted. Patients received pregabalin 300mg/day, venlafaxine XR 75 mg/day or placebo for a week, followed by pregabalin 300–600mg/day, venlafaxine XR 75–225 mg/day, or placebo for 7 weeks. Treatment effect on sleepwas evaluated using the Medical Outcomes Study Sleep Scale. Anxiety symptoms were assessedwith the Hamilton Anxiety Rating Scale. A mediation model was used to estimate separatelyfor both treatment arms the direct and indirect treatment effects on sleep disturbance.Results: Compared with placebo (n = 128), treatment with pregabalin (n = 121) significantlyreduced scores on the sleep disturbance subscale and Sleep Problems Index II atboth week 4 and week 8, and the sleep adequacy subscale at week 8. Venlafaxine XR (n =125) had no significant effect on these measures. The mediation model indicated that 53%of the total pregabalin effect on sleep disturbance was direct (p < 0.01) and 47% indirect,mediated through anxiety symptoms (p < 0.05).Conclusions: Pregabalin decreased sleep disturbance in patients with GAD both directly,and indirectly by reducing anxiety symptoms. Given the drug specificity of the results,this study provides evidence of an additional important pathway of action for pregabalinand its efficacy in GAD (AU)

The cardiovascular and subjective effects of methamphetamine combined with gamma-vinyl-gamma-aminobutyric acid (GVG) in non-treatment seeking methamphetamine-dependent volunteers.

Gamma-vinyl-gamma-aminobutyric acid (GVG) elevates central nervous system gamma-aminobutyric acid (GABA) levels by irreversibly inhibiting GABA transaminase. An open-label clinical trial in humans suggested that GVG may reduce cocaine and methamphetamine use. To test safety and to obtain preliminary data on efficacy of GVG for treating methamphetamine dependence, we conducted a double-blind, placebo-controlled, parallel group study of GVG interaction with the cardiovascular and subjective effects produced by methamphetamine. Non-treatment seeking methamphetamine-dependent volunteers received either GVG (N=8) or placebo (N=9) by random assignment. GVG treatment was initiated at 1 g/day and increased to 5 g/day. After reaching the target dose of 5 g/day, participants received methamphetamine (15+30 mg, IV), and cardiovascular and subjective effects were assessed. No serious adverse events were noted, and the total number of adverse events was similar between the treatment groups. Considering the full time course and peak effects independently, no significant differences were detected between the groups for systolic or diastolic blood pressures, or heart rate, following methamphetamine exposure. Some methamphetamine-induced cardiovascular changes approached significance (p<0.10) and may warrant attention in future trials. Methamphetamine-induced subjective effects ("any drug effect", "high", "crave methamphetamine") were statistically similar between GVG and placebo treatment groups. Pharmacokinetic data indicate that GVG treatment did not alter methamphetamine or amphetamine plasma levels, and there was no association between methamphetamine or amphetamine plasma levels and peak cardiovascular effects. Taken together, the data indicate that GVG treatment is generally well tolerated but not efficacious in attenuating the positive subjective effects of methamphetamine in the laboratory.

Effects of a dopamine receptor agonist and atropine sulfate on absorption of valproic acid in rats.

The aim of this study is to determine whether pramipexole hydrochloride hydrate (PHH) and atropine sulfate affect valproic acid (VPA) pharmacokinetics and to evaluate how plasma VPA concentrations are altered by different PHH administration routes. The following studies were conducted on rats: 1) changes in plasma VPA concentration after simultaneous oral administration (PO) of PHH and VPA-Na; 2) effects of intraperitoneal administration (IP) of PHH on plasma VPA concentration after VPA-Na PO; 3) effects of PHH PO on plasma VPA concentration after intravenous administration (IV) of VPA-Na; and 4) changes in plasma VPA concentration after simultaneous PO of atropine sulfate and VPA-Na. Atropine sulfate PO significantly decreased the area under the concentration-time curve up to 3 h (AUC0-3, the total amount of drug plasma concentration) of VPA, suggesting that atropine sulfate decreases VPA-Na absorption probably due to reduced gastrointestinal motility by its anticholinergic action. Similarly, by PHH PO or IP, VPA AUC0-3 was significantly decreased. However, in cases of VPA-Na IV, all VPA parameters were unchanged by PHH PO. These results indicate that the PHH inhibitory effect may be caused in the absorption phase of VPA by pharmacological action of PHH, and thus PHH decreases VPA-Na bioavailability.

Gabapentina en el tratamiento de la neuromiotonía ocular / Gabapentin in the treatment of ocular neuromyotonia

No disponible

No disponible

Eficacia de la gabapentina en el tratamiento del síndrome del túnel carpiano / Efficacy of gabapentin in the treatment of carpal tunnel syndrome

Fundamento y objetivo: Evaluar la eficacia analgésica y la seguridad de la gabapentina en el tratamiento del síndrome del túnel carpiano (STC), así como la evolución electromiográfica (EMG) a los 6 meses. Pacientes y método: Estudio prospectivo de 6 meses de duración en los pacientes con diagnóstico EMG de STC primario en tratamiento con gabapentina a dosis de 1.800 mg/día. En la visita basal y a los 6 meses se realizaron valoración clínica, exploración y EMG, y se registraron los efectos adversos. Resultados: Se incluyó en el estudio a 25 pacientes con una edad media (desviación estándar) de 58,88 (7,69) años. A los 6 meses se observó una reducción del dolor (p = 0,001) y de la intensidad de los síntomas (p = 0,008), sin cambios en la capacidad funcional. El EMG se realizó a los 6 meses en 19 pacientes, de los que no se observaron cambios respecto a EMG basal en un 52,6%, se apreció mejoría en un 5,3%, progresión en un 15,8% y curación en un 26,3%. En un 28% se retiró el tratamiento por efecto adverso. Conclusiones: En nuestra serie la gabapentina fue eficaz en la reducción del dolor y en la mejoría de la intensidad de los síntomas. El EMG a los 6 meses de tratamiento demostró estabilidad, mejoría y/o curación en el 84,2% de los casos. La gabapentina resultó segura y bien tolerada

Background and objective: To evaluate the analgesic efficacy and safety of gabapentin in the treatment of carpal tunnel syndrome (CTS), as well as the electromyographic (EMG) evolution after 6 months. Patients and method: A prospective study with a 6-month follow-up of patients with EMG diagnosis of primary CTS starting treatment with 1.800 mg/day of gabapentin. At baseline visit and after 6 months of treatment a complete clinical evaluation and an EMG study were performed. Adverse effects of gabapentin were also registered. Results: Twenty-five patients were included, mean age (standard deviation) 58.88 (7.69) years. After 6 months of treatment, a statistically significant reduction of pain (p = 0.001) and improvement of severity of symptoms (p = 0.008) were observed, although functional capacity did not change. EMG was performed in 19 patients at 6 months. Compared to baseline EMG: 52.6% patients showed no changes in EMG findings, while 5.3% patients showed improvement and in 26.3% the EMG was normal. Progression was only seen in 15.8% of patients after 6 months of treatment. In 28% of the patients gabapentin was stopped because of side effects. Conclusions: In our series, gabapentin was effective in the reduction of pain and improvement of the severity of the symptoms. Results of EMG after 6 months of treatment showed no changes, with improvement and/or remission in 84.2% of the cases. The drug was safe and well tolerated

Uptake and release of [(3)H]GABA in human dental pulp.

The purpose of this study was to determine whether (a) an uptake system for gamma-aminobutyric acid (GABA) exists in human dental pulp, (b) GABA can be released from nerves in this tissue, and (c) GABA(B) autoreceptors modulate release of this transmitter. Segments of vital pulp were incubated in [(3)H]GABA (0.1-10 microM) for up to 120 min, washed, and the retained [(3)H] extracted and assayed. Some tissues were treated with GABA uptake inhibitors (nipecotic acid or NO-711) prior to incubation. At concentrations of 0.1 and 1.0 microM the uptake of [(3)H]GABA was saturated after 90 min of incubation. At 10 microM, at least two uptake compartments were apparent, and the amount of [(3)H]GABA retained was five-fold greater than 0.1 microM. The uptake inhibitors reduced [(3)H]GABA accumulation by more than 80%. In the release study, pulp was incubated in [(3)H]GABA (0.5 microM) for 90 min, and superfused with Krebs solution containing NO-711 (5 microM). Electrical stimulation increased the overflow of [(3)H]; a GABA(B) autoreceptor agonist (baclofen) inhibited, whilst an antagonist, Sch 50911, enhanced this release. The effects of baclofen were reversed by Sch 50911. These results imply that GABA can be taken up and bound firmly in compartments within human dental pulp, GABA can be released from isolated pulp segments by electrical stimulation, and this release is modulated by GABA(B) autoreceptors.

Eficacia de la gabapentina en el tratamiento del dolor neuropático secundario a la lesión medular / Efficacy of the gabapentine in the treatment of the neuropathic pain due to spinal cord injury

en el tratamiento del dolor neuropático en pacientes afectos de lesión medular. Pacientes y métodos: Estudio prospectivo y comparativo en el que se incluyeron pacientes con lesión medular y dolor neuropático de acuerdo con la clasificación de Siddall y definición de la IASP, de más de tres meses de evolución y que no hubieran recibido tratamiento previo con gabapentina. Se valoraron y cuantificaron las características e intensidad del dolor neuropático y su interferencia con el sueño, así como su tolerabilidad a través de visitas seriadas. Resultados: Fueron incluidos 43 pacientes, 80,5 % varones con una edad media de 42 + 10,2 años. Se apreció mejoría en la descripción, valoración e intensidad del dolor en las escalas de Lattinen y McGill (p< 0,0001); así como en la interferencia con el sueño (p<0,0001) entre las dos visitas de seguimiento. La tolerabilidad del medicamento fue calificada como excelente en el 73,8%. Conclusiones: El tratamiento del dolor neuropático secundario a la lesión medular con gabapentina ofrece resultados satisfactorios en cuanto a la reducción de la intensidad y frecuencia del mismo; consigue disminuir la interferencia que produce en el sueño y constituye una alternativa segura, con pocos efectos secundarios

Objective: To evaluate the efficacy and tolerability of gabapentin in the treatment of neuropathic pain in patients with spinal cord injury. Patients and methods: Prospective and comparative study was designed. Individuals with spinal cord injury and neuropathic pain in accord with Siddall's classification and IASP's definition were included. The evolution of pain was longer than three moths and any patient had received previously treatment with gabapentine. Intensity and characteristic of neurophatic pain and its interference with sleep were measured and the tolerability was also assessed. Results: Fourty three patients were included, 80,5% men, 42+10,2 years aged. The results of description and intensity of pain in Lattinen and McGill scales were better (p<0,001), as also the interference with sleep (p<0,001) between the visits of control. Conclusions: The treatmet of neurophatic pain due to spinal cord with gabapentine offers satisfactory results to decrease its intensity and frecuency, to get a lower interference with sleep and it is a safe alternative with very few secundary effects

Anxiolytic-like activity of SB-205384 in the elevated plus maze test in mice / Actividad ansiolítica del sb-205384 en el laberinto elevado en cruz en ratones

Recent studies point to a major role for a2-containing GABA-A receptors in modulating anxiety. However, the possible implication of GABA-A receptors containing the a3 subunit on anxiety is less known. The aim of this study was to examine the effects of SB-205384 (0.5-4 mg/kg, ip), an a3 subunit positive modulator of GABA-A receptor, on anxiety tested in the elevated plus-maze in male mice, using classical and ethological parameters. Mice treated with SB-205384 showed an increase in the frequency of entries and the time spent in open arms, as well as a reduction in the time spent in closed arms, as compared with the control group. A notable increase of «head-dipping» unprotected and a reduction of «stretched-attend posture» protected was also evident. These findings indicate that SB-205384 exhibits an anxiolytic-like profile in the elevated plus-maze test, suggesting that GABA-A receptors which contain the a3 subunit might be involved in regulation anxiety

Recientes investigaciones indican que los receptores GABA-A que contienen subunidades a2 desempeñan un importante papel en la modulación de la ansiedad. Sin embargo, la posible implicación de los receptores GABA-A que contienen la subunidad a3 es menos conocida. El objetivo de este trabajo fue examinar los efectos del SB-205384 (0.5-4 mg/kg, ip), un modulador positivo de los receptores GABA-A que contienen la subunidad a3, sobre la ansiedad evaluada en el laberinto elevado en cruz en ratones machos, utilizando parámetros clásicos y etiológicos. Los animales tratados con SB-205384 mostraron un incremento en la frecuencia de entradas y el tiempo pasado en brazos abiertos, así como una reducción en el tiempo pasado en los brazos cerrados del laberinto, en comparación con el grupo control. Igualmente, se observó un notable aumento en la frecuencia de «head-dipping» desprotegidos y una disminución del número de «stretched-attend posture» protegidos. Estos resultados indican que el SB-205384 exhibe un perfil ansiolítico en el test de laberinto elevado en cruz, sugiriendo que los receptores GABA-A que contienen la subunidad a3 podrían estar involucrados en la regulación de la ansiedad

Medida de la calidad de vida mediante las láminas Coop-Wonca en una muestra de pacientes con fibromialgia tratadas con pregabalina / No disponible

Objetivo: En el seguimiento de los enfermos de Fibromialgia interesa conocer los resultados obtenidos en medidas que reflejen la repercusión sobre la Calidad de Vida Relacionada con la Salud (CVRS) de los pacientes. Este interés aumenta cuando se utiliza un fármaco novedoso como es pregabalina, un anticonvulsivante de última generación, que se une a la subunidad a2-d de los canales del calcio. Utilizando como instrumento las láminas COOP-WONCA ( versión validada española de Nottingham Health Profile ) nos planteamos estudiar si pregabalina mejora la percepción de calidad de vida de un grupo de pacientes con Fibromialgia. Métodos: Este estudio comparó los resultados de las láminas Coop-Wonca sin pregabalina, con pregabalina a dosis de 300 y de 600 mg/día en un grupo de 16 pacientes con Fibromialgia. En todos los casos se mantuvieron sus tratamientos habituales. Resultados: No hubo diferencias estadísticamente significativas en los resultados de las láminas Coop-Wonca al añadir pregabalina a dosis de 300 mg/día y 600 mg/día ( p ‹ 0.05 ). Los efectos secundarios más frecuentes fueron mareo y aumento de peso. Conclusión: Las viñetas Coop-Wonca como instrumento de medida la calidad de vida relacionada con la salud no mostraron mejoría en nuestra muestra de 16 pacientes con FM cuando se añadió pregabalina al tratamiento. Creemos que se precisa un estudio más amplio con un número mayor de pacientes para extraer más conclusiones al respecto (AU)

Objective: About the evolution of patients with Fibromyalgia it is interesting to know the results of measures assesing of the health-related quality of life.The interest annhace with the use of a new drug, pregabalin, the lastest generation anti-convulsivant, a ligand of a2-d subunit of calcium chanels. Helped by the COOP-WONCA charts ( reliable Spanish version of Nottingham Health Profile) our aim is determine if pregabalin improve the health-related quality of life in a group of Fibromyalgia affected patients. Methods: This trial compared the results of Coop-Wonca charts without pregabalin, with dosis of 300 and 600 mg/day pregabalin in a group of 16 patients with Fibromyalgia. All patients were continuated with their medications. Results: Pregabalin at 300 and 600 mg/day did not significantly improvement in the results of Coop/Wonca charts (p ‹ 0.05). Dizziness and weight gain were the most frequent adverse events. Conclusion: The scale of health-related quality of life Coop/Wonca did not result in improvement in our group of 16 patientes with Fibromyalgia when pregabalin was add to the treatment. Further study with a large group of patients is necessary to draw more conclusions on this point (AU)

Efectividad de la gabapentina en el tratamiento de la espasticidad: estudio aleatorizado, a doble ciego y controlado con placebo / Gabapentin for spasticity: a randomized, double-blind, placebo-controlled trial

FUNDAMENTO Y OBJETIVO: Demostrar la eficacia y seguridad de la gabapentina en el tratamiento de la espasticidad asociada al síndrome de motoneurona superior. PACIENTES Y MÉTODO: En este ensayo de doble ciego piloto, de 10 semanas de duración, se aleatorizó a 30 pacientes con lesiones en el tracto piramidal para recibir hasta 3.600 mg/día de gabapentina (n = 15) o placebo (n = 15). La variable principal fue el valor de la escala de Ash-worth. Las variables secundarias fueron la escala de frecuencia de espasmos, la amplitud máxima de movimientos, el índice de amplitud H/M, el índice de Barthel para la calidad de vida y los acontecimientos adversos. La evaluación de los datos se ha realizado mediante un análisis por intención de tratar. RESULTADOS: El grupo gabapentina presentó una mejora significativa de los valores totales de laescala de Ashworth y de los valores para grupos de músculos individuales afectados. No se observarondiferencias significativas para el valor total de la escala de frecuencia de espasmos entre los 2 grupos; sin embargo, la gabapentina resultó eficaz en todas las visitas al analizar los grupos de músculos afectados individualmente. La gabapentina no modificó los valores de la amplitud de movimientos, el índice de amplitud H/M ni el índice de Barthel. No se observó ninguna alteración de la marcha ni del desplazamiento durante el tratamiento con gabapentina. Los acontecimientos adversos relacionados ocurrieron con menor frecuencia en el grupo gabapentina, y menos pacientes tratados con ésta tuvieron que abandonar la medicación por losacontecimientos adversos. CONCLUSIONES: La gabapentina en dosis de 2.700 a 3.600 mg/día es eficaz y segura para el tratamiento de la espasticidad asociada al síndrome de la motoneurona superior

BACKGROUND AND OBJECTIVE: We aimed to demonstrate the efficacy and safety of gabapentin forthe treatment of spasticity in patients with upper motor neuron syndrome. PATIENTS AND METHOD: Thirty patients with pyramidaltract lesions were randomized to up to3,600 mg/day of gabapentin (n = 15) or placebo (n = 15) in a double-blind, pilot 10-week trial. The primary efficacy variable was the Ashworth Scale score. Secondary variables included the Spasm Frequency Scale, maximal range of movement, H/M Amplitude Ratio, and the Barthel Index for quality of life. Adverse events were recorded. All data were analyzed on an intent-to-treat basis. RESULTS: Demographic and baseline characteristics were similar between the 2 treatmentgroups. The gabapentin group showed significant improvement in Ashworth Scale total scores, and scores for individual affected muscle groups. Fifteen of the randomized patients had spasms; the total Spasm Frequency Scale score was not significantly different between groups. Nevertheless, when affected individual muscle groups were analyzed, a significant effect of gabapentin vs placebo was observed at all visits. Gabapentin did not modify the scores of the ran-geof movement, the H/M Amplitude Ratio, or the Barthel Index tests. No gait or displacement impairment were seen during treatment with gabapentin. Related adverse events occurred less frequently in the gabapentin group, and fewer gabapentin patients withdrew because of adverseevents. CONCLUSIONS: Gabapentin demonstrated efficacy and safety at doses between 2,700 and 3,600mg/day as a therapy for the spasticity associated with the upper motor neuron syndrome