Effect of preoperative gabapentin on pain intensity and development of chronic pain after carpal tunnel syndrome surgical treatment in women: randomized, double-blind, placebo-controlled study / Efeito da gabapentina pré-operatória na intensidade da dor e desenvolvimento de dor crônica após o tratamento cirúrgico da síndrome do túnel do carpo em mulheres: estudo randomizado duplo-cego controlado com placebo

ABSTRACT CONTEXT AND OBJECTIVES: Effective postoperative analgesia is important for reducing the incidence of chronic pain. This study evaluated the effect of preoperative gabapentin on postoperative analgesia and the incidence of chronic pain among patients undergoing carpal tunnel syndrome surgical treatment. DESIGN AND SETTINGS: Randomized, double-blind controlled trial, Federal University of São Paulo Pain Clinic. METHODS: Forty patients aged 18 years or over were randomized into two groups: Gabapentin Group received 600 mg of gabapentin preoperatively, one hour prior to surgery, and Control Group received placebo. All the patients received intravenous regional anesthesia comprising 1% lidocaine. Midazolam was used for sedation if needed. Paracetamol was administered for postoperative analgesia as needed. Codeine was used additionally if the paracetamol was insufficient. The following were evaluated: postoperative pain intensity (over a six-month period), incidence of postoperative neuropathic pain (over a six-month period), need for intraoperative sedation, and use of postoperative paracetamol and codeine. The presence of neuropathic pain was established using the DN4 (Douleur Neuropathique 4) questionnaire. Complex regional pain syndrome was diagnosed using the Budapest questionnaire. RESULTS: No differences in the need for sedation, control over postoperative pain or incidence of chronic pain syndromes (neuropathic or complex regional pain syndrome) were observed. No differences in postoperative paracetamol and codeine consumption were observed. CONCLUSIONS: Preoperative gabapentin (600 mg) did not improve postoperative pain control, and did not reduce the incidence of chronic pain among patients undergoing carpal tunnel syndrome surgery.

RESUMO CONTEXTO E OBJETIVOS: Analgesia pós-operatória eficaz é importante para reduzir a incidência de dor crônica. Este estudo avaliou o efeito da gabapentina pré-operatória na analgesia pós-operatória e na incidência de dor crônica em pacientes submetidos à cirurgia para tratamento da síndrome do túnel do carpo. DESENHO E LOCAL: Randomizado, duplo cego, Universidade Federal de São Paulo. MÉTODOS: Os 40 pacientes com 18 anos ou mais de idade foram distribuídos aleatoriamente em dois grupos: o Grupo Gabapentina recebeu 600 mg de gabapentina no pré-operatório uma hora antes da cirurgia, e o Grupo Controle recebeu placebo. Todos os pacientes receberam anestesia regional intravenosa com lidocaína a 1%. Midazolam foi utilizado para sedação, se necessário. Paracetamol foi administrado para analgesia pós-operatória, conforme necessário, e codeína, se o paracetamol fosse insuficiente. Foram avaliados: a intensidade da dor pós-operatória (durante seis meses), a incidência de dor neuropática pós-operatória (durante seis meses), a necessidade de sedação intra-operatória e o uso de paracetamol e codeína no pós-operatório. A presença de dor neuropática foi estabelecida utilizando-se o questionário DN4 (dor neuropática 4). Síndrome de dor regional complexa foi diagnosticada através do questionário Budapeste. RESULTADOS: Não foram observadas diferenças na necessidade de sedação, no controle da dor pós-operatória e na incidência de síndromes dolorosas crônicas (neuropáticas ou síndrome de dor regional complexa). Não foram observadas diferenças no consumo de paracetamol e codeína. CONCLUSÕES: Gabapentina pré-operatória (600 mg) não melhorou o controle da dor pós-operatória e não reduziu a incidência de dor crônica em pacientes submetidos à cirurgia para tratamento da síndrome do túnel do carpo.

Efectividad y seguridad de gabapentina y pregabalina como monoterapia de primera línea en adultos con dolor neuropático / Effectiveness and safety of gabapentin and pregabalin as first-line monotherapy in adults with neuropathic pain

Antecedentes: Descripción de la condición de salud de interés: La Asociación Internacional del Estudio del Dolor en el año 2011 definió el dolor neuropático como una afección neurológica crónica causado por una lesión o enfermedad del sistema nervioso. Se debe a una lesión o mal funcionamiento del sistema nervioso, a un daño del nervio en sí (u otra parte del sistema sensorial) y no a una activación anormal de las vías nociceptoras. El mecanismo generador del dolor neuropático se halla en cualquier sitio a lo largo del recorrido de las vías nociceptivas (las vías que conducen la información de tipo doloroso), sin estimular inicialmente a los nociceptores (los receptores de dolor), a diferencia de lo que sucede con el dolor nociceptivo o fisiológico. Descripción de las tecnologías: Gabapentina y pregabalina son medicamentos anticonvulsivantes empleados en el tratamiento del dolor neuropático; a ctúan disminuyendo la liberación de neurotransmisores excitadores, lo que reduce la entrada de calcio en las terminaciones nerviosas. Las dos tecnologías tienen registro sanitario INVIMA para la indicación de interés. Evaluación de efectividad y seguridad: Pregunta de evaluación: En adultos con dolor neuropático, ¿cuál es la efectividad y seguridad de gabapentina y pregabalina comparadas con amitriptilina, oxcarbazepina, duloxetina, tramadol (sólo o en combinaciones) o lidocaína en parches, como monoterapia de primera línea para el alivio del dolor? La pregunta de evaluación fue refinada y validada con base en: autorización de mercadeo de \r\nlas tecnologías para la indicación de interés (registro sanitario INVIMA), listado de medicamentos vitales no disponibles, cobertura de las tecnologías en el Plan Obligatorio de Salud (POS) (Acuerdo 029 de 2011), revisión de grupos terapéuticos (clasificación ATC: Anatomical, Therapeutic, Chemical classification system), recomendaciones de guías de práctica clínica actualizadas, disponibilidad de evidencia sobre efectividad y seguridad (reportes de evaluación de tecnologías y revisiones sistemáticas de la literatura), uso de las tecnologías (listas nacionales de recobro, estadísticas de prescripción, etc), \r\nestudios de carga de enfermedad y consulta con un experto temático (especialista clínico). No se dentificaron otros comparadores relevantes para la evaluación. Población: Adultos con dolor neuropático tipo: Neuropatía diabética periférica; Neuralgia posherpética; Dolor neuropático asociado con lesión de la médula espinal. \r\nLa población se refinó después de revisar la evidencia disponible, considerando además, que los efectos de las tecnologías bajo evaluación podrían diferir entre pacientes con distintos tipos de dolor neuropático. Metodología: Búsqueda de literatura, Búsqueda en bases de datos electrónicas. Conclusiones: En pacientes con neuropatía diabética periférica, gabapentina es una opción con ventajas en efectividad, sin ventajas en seguridad y tolerabilidad. En la misma población, pregabalina sin discriminar por dosis no tiene ventajas en efectividad; en dosis ≥ 300 mg es una opción con ventajas en efectividad, no es segura y no presenta ventajas en tolerabilidad; para dosis ≤ 150 mg la evidencia sobre su efectividad no es concluyente, no presenta ventajas en cuanto a seguridad y tolerabilidad. En pacientes con neuralgia posherpética, la evidencia sobre la efectividad de gabapentina no es concluyente, para el mismo tipo de dolor, pregabalina es una opción desfavorable en términos de efectividad y de seguridad a altas dosis. En pacientes con dolor neuropático asociado con lesión de la médula espinal no se identificó evidencia sobre la efectividad de gabapentina o pregabalina. En la misma población, gabapentina no tiene ventajas en tolerabilidad, por su parte, pregabalina no es segura y no presenta ventajas en tolerabilidad. La calidad de la evidencia para las comparaciones de interés y desenlaces descritos es alta.

Efficacy of perioperative pregabalin in acute and chronic post-operative pain after off-pump coronary artery bypass surgery: A randomized, double-blind placebo controlled trial.

Aims and Objectives: We evaluated the efficacy of perioperative pregabalin on acute and chronic post-operative pain after off-pump coronary artery bypass (OPCAB) surgery. Materials and Methods: Forty patients undergoing elective OPCAB surgery were randomized to pregabalin and control groups. Pregabalin group received 150 mg pregabalin 2 h prior to induction of anesthesia and 75 mg twice daily for 2 post-operative days whereas the control group received placebo at similar timings; pregabalin and placebo were administered by an anesthesiologist blinded to the drugs. Pain scores (visual analogue scale [VAS]) and sedation scores were observed at 0, 4, 6, 12, 24, 36 and 48 h after extubation. Time to extubation, tramadol consumption and side-effects were noted. VAS score was analyzed by Mann-Whitney U test. The analysis of variance test for repeated measures was used for comparison of the means of continuous variables. Group comparisons were made using the Chi-square-test. Results: Pain-scores at 6, 12, 24 and 36 h from extubation at rest and at deep breath were less in pregabalin treated patients ( P < 0.05). Tramadol consumption was reduced by 60% in pregabalin group ( P < 0.001). Extent of sedation, extubation times and incidence of nausea were comparable. The effect on chronic post-operative pain was not significant. Conclusions: Perioperative pregabalin reduced pain scores at rest and deep breath and reduced consumption of tramadol in the post-operative period without delaying extubation and causing excessive sedation.

Efficacy of Combination of Meloxicam and Pregabalin for Pain in Knee Osteoarthritis

PURPOSE: Osteoarthritic pain is largely considered to be inflammatory pain. Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis (OA) in which the subchondral bone junction is destroyed, and this induces neuropathic pain (NP). Pregabalin was developed as a pain killer for NP; however, there are no reports on pregabalin use in OA patients. The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients. MATERIALS AND METHODS: Eighty-nine knee OA patients were evaluated in this randomized prospective study. Patients were divided into meloxicam, pregabalin, and meloxicam+pregabalin groups. Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain scales among groups were compared using a Kruskal-Wallis test. RESULTS: Before drug application, there was no significant difference in VAS and WOMAC scores among the three groups (p>0.05). Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1, 2, and 4 weeks, and WOMAC score at 4 weeks, compared with the other groups (p0.05). CONCLUSION: Meloxicam+pregabalin was effective for pain in OA patients. This finding suggests that OA pain is a combination of inflammatory and NP.

effects of gabapentin on methadone based addiction treatment: a randomized controlled trial

Gabapentin is a potentially useful drug in alleviating the hyperexcitatory painful states in the control of opiate dependence in acute detoxification and the stabilization phase. This study aim was to evaluate the effectiveness of gabapentin adds-on methadone therapy on lowering the methadone. This randomized double blind controlled clinical trial conducted at an outpatient rehabilitation clinic. Sixty patients using opium, opium extract and heroin were randomly assigned to two groups [34 in treatment group and 26 in control group]; one group was prescribed combination of methadone [40-120 mg] and gabapentin [300 mg] as group A, and the other group was given methadone [40-120] and placebo as group B. The subjects were followed up for three weeks after intervention. There were 60 outpatients including 51 males with the mean age of 40.9 +/- 9.2. Daily dose and cumulative dose of methadone during the treatment was found to be significantly higher in group B [73.8 +/- 19.5 mg daily vs. 58.9 +/- 11 mg daily and cumulatively 1550.7 +/- 409.7 mg vs. 238.3 +/- 238.2 mg, p= 0.001]. When the patients were stratified based on the kind of abused drug, the methadone dose was seen to be significantly reduced in the opium addicted patients in the group A. Group A showed more withdrawal symptoms whereas the most common complain of group B was sedation particularly during the first three days. The results showed that gabapentin is an effective adds-on therapy when is added to methadone. This drug leads to relief of withdrawal symptoms and lower methadone consumption

[ effect of a single dose of gabapentin on the rate of consumption of propofol and remifentanil during total intravenous anesthesia]

Gabapentin [structural analog of GABA], is an antiepileptic drug that its preoperative administration results in postoperative pain reduction. Considering the hypnotic effect of propofol, which is mediated by its attachment to GABAA, this hypothesis was propounded that administration of gabapentin can probably decrease the need for propofol and remifentanil during total intravenous anesthesia. Fifty patients scheduled for elective laparoscopic cholecystectomy, were assigned into two equal groups [n=25] in this randomized double blinded clinical trial. Study group received oral gabapentin [1200mg], and control group received placebo 3hrs before operation. Premedication and induction of anesthesia were the same in all patients. For the maintenance of anesthesia, oxygen and nitrous oxide [50%-50% mixture] and propofol and remifentanil infusion were used. The rate of propofol infusion was adjusted to maintain BIS in the range of 40- 60, and dose of remifentanil adjusted to maintain hemodynamic variables in the range of +/- 20% of baseline values. At the end of anesthesia the duration of anesthesia and the total amount of propofol and remifentanil used for every patient were recorded. The demographic parameters were similar in both groups [p>0.05]. Doses of propofol and remifentanil used for study group were significantly lower than doses used for control group [p<0.01]. The mean values of baseline systolic, diastolic, mean arterial, heart rates and BIS in the study group were lower than the corresponding values in the control group [p<0.05]. This study showed that a single dose of gabapentin before operation can decrease the need for propofol and remifentanil in total intravenous anesthesia during laparoscopic cholecystectomy

Effects of preoperative gabapentin on postoperative nausea and vomiting after open cholecystectomy: a prospective randomized double-blind placebo-controlled study

To evaluate the effect of gabapentin on the incidence and severity of postoperative nausea and vomiting [PONV] after open cholecystectomy. A total of 90 patients scheduled for elective open cholecystectomy were randomly assigned to either a gabapentin group [600 mg, 2 h before surgery] or a placebo group. For the analysis, 1 patient was excluded from the gabapentin group and 2 patients from the placebo group. A standard technique was used for anesthesia. Pethidine and metoclopramide were used for postoperative management of pain and nausea/vomiting, respectively. The prevalence of PONV, its severity [measured on visual analogue scale, VAS], and total pethidine and metoclopramide use in the first 24 h after the operation were recorded. There were no demographic differences between the two groups. Of the 44 patients given gabapentin, 16 [36.6%] and 28 of 43 [65.2%] placebo patients developed PONV; the difference was statistically significant [p = 0.02]. However, there was no difference in the severity of PONV between the gabapentin and placebo groups [p = 0.12]. Gabapentin patients used less pethidine [28.33 +/- 129 mg] and metoclopramide [6.0 +/- 6.3 mg] than the placebo group [35.1 +/- 15.1 and 9.33 +/- 7.1 mg, respectively]. The differences were statistically significant [pethidine: p = 0.002, metoclopramide: p = 0.033]. However, gabapentin did not reduce postoperative pain significantly [p = 0.096]. Our data show that gabapentin not only reduced PONV after open cholecystectomy, but also reduced the need for additional postoperative analgesics

Protective Effects of Gabapentin on Allodynia and alpha2delta1-Subunit of Voltage-dependent Calcium Channel in Spinal Nerve-Ligated Rats

This study was designed to determine whether early gabapentin treatment has a protective analgesic effect on neuropathic pain and compared its effect to the late treatment in a rat neuropathic model, and as the potential mechanism of protective action, the alpha2delta1-subunit of the voltage-dependent calcium channel (alpha2delta1-subunit) was evaluated in both sides of the L5 dorsal root ganglia (DRG). Neuropathic pain was induced in male Sprague-Dawley rats by a surgical ligation of left L5 nerve. For the early treatment group, rats were injected with gabapentin (100 mg/kg) intraperitoneally 15 min prior to surgery and then every 24 hr during postoperative day (POD) 1-4. For the late treatment group, the same dose of gabapentin was injected every 24 hr during POD 8-12. For the control group, L5 nerve was ligated but no gabapentin was administered. In the early treatment group, the development of allodynia was delayed up to POD 10, whereas allodynia was developed on POD 2 in the control and the late treatment group (p<0.05). The alpha2delta1-subunit was up-regulated in all groups, however, there was no difference in the level of the alpha2delta1-subunit among the three groups. These results suggest that early treatment with gabapentin offers some protection against neuropathic pain but it is unlikely that this action is mediated through modulation of the alpha2delta1-subunit in DRG.

The Interaction of Gabapentin and N(6)-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA) on Mechanical Allodynia in Rats with a Spinal Nerve Ligation

We examined the antiallodynic interaction between gabapentin and adenosine A1 receptor agonist, N(6)-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA), in a rat model of nerve ligation injury. Rats were prepared with ligation of left L5-6 spinal nerves and intrathecal catheter implantation for drug administration. Mechanical allodynia was measured by applying von Frey filaments. Gabapentin and R-PIA were administered to obtain the dose-response curve and the 50% effective dose (ED50). Fractions of ED50s were administered concurrently to establish the ED50 of the drug combination. The drug interaction between gabapentin and R-PIA was analyzed using the isobolographic method. Adenosine A1 receptor antagonist was administered intrathecally to examine the reversal of the antiallodynic effect. Locomotor function changes were evaluated by rotarod testing. Intrathecal gabapentin and R-PIA and their combination produced a dose-dependent antagonism against mechanical allodynia without severe side effects. Intrathecal gabapentin synergistically enhanced the antiallodynic effect of R-PIA when coadministered. There were no significant changes in rotarod performance time, except gabapentin 300 microgram. In the combination group, the maximal antiallodynic effect was reversed by A1 adenosine receptor antagonist. These results suggest that activation of adenosine A1 receptors at the spinal level is required for the synergistic interaction on the mechanical allodynia.

The antidotal effects of high-dosage gamma-aminobutyric acid on acute tetramine poisoning as compared with sodium dimercaptopropane sulfonate / 华中科技大学学报（医学）（英德文版）

To investigate the therapeutic effect of high-dosage gamma-aminobutyric acid (GABA) on acute tetramine (TET) poisoning, 50 Kunming mice were divided into 5 groups at random and the antidotal effects of GABA or sodium dimercaptopropane sulfonate (Na-DMPS) on poisoned mice in different groups were observed in order to compare the therapeutic effects of high-dosage GABA with those of Na-DMPS. Slices of brain tissue of the poisoned mice were made to examine pathological changes of cells. The survival analysis was employed. Our results showed that both high-dosage GABA and Na-DMPS could obviously prolong the survival time, delay onset of convulsion and muscular twitch, and ameliorate the symptoms after acute tetramine poisoning in the mice. Better effects could be achieved with earlier use of high dosage GABA or Na-DMPS. There was no significant difference in prolonging the survival time between high-dose GABA and Na-DMPS used immediately after poisioning. It is concluded that high-dosage GABA can effectively antagonize acute toxicity of teramine in mice. And it is suggested that high-dosage GABA may be used as an excellent antidote for acute TET poisoning in clinical practice. The indications and correct dosage for clinical use awaits to be further studied.

La insulinoterapia intensificada más antineuríticos es superior a antineurítico puro en neuropatía diabética dolorosa / Intensified insulin therapy plus antineuritic medication is more effective than antineuritics alone in painful diabetic neuropathy

Background: The basis of the treatment of painful diabetic neuropathy is the use of drugs that block the transmission of pain (antineuritics) and a good metabolic control of underlying disease. Aim: To describe the outcomes of 17 type-2 diabetics with painful neuropathy, treated between 1988 and 2005 with symptomatic therapy plus intensified insulin. Material and methods: Review of medical records of 17 type-2 diabetic patients, aged 63±11 years and a duration of diabetes of 15±8 years. All patients received intensified insulin therapy with 0.35 units/kg of NPH insulin (2/3 before breakfast and 1/3 evening meal), plus capillary glucose measurements and regular insulin (with sliding-scale centered in ~0.1 units/kg) before the 3 main meals. All patients were also treated with gabapentin, nortriptyline or clomipramine. Pain was assessed using a visual analog score of 10 points. Results: After 1 year, glycosilated hemoglobin decreased from 10.0±1.4 percent to 7.7±1.2 percent (p~=0.003). Pain decreased from 10 to 5.1±3.3 at one month, 2.3±3.2 at six months, and 3.1±3.6 at 1 year (p <0.01). There was a direct statistical correlation between the reduction of HbA1C and pain decline (r =0.736; p =0.037). Pain scores were lower than those reported elsewhere for Pregabalin (n =76; p =0.05), Lamotrigine (n =27; p <0.0005), Topiramate (n =208; p <0.005), and Gabapentin (n =84; p <0.025). The lack of difference to Sodium Valproate (n =21; p =0.07) had borderline significance. Conclusions: The addition of intensified insulin therapy to the symptomatic treatment of painful neuropathy in type-2 diabetics, significantly enhanced the reduction of pain. The lowering of glycosilated hemoglobin was a significant predictor of success in pain reduction.

Antinociceptive Interactions between Intrathecal Gabapentin and MK801 or NBQX in Rat Formalin Test

Antagonists for spinal N-methyl-D-aspartate (NMDA) and amino-hydroxy-methtyl-isoxazolepropionate (AMPA) receptors are effective in attenuating acute nociception or injury-induced hyperalgesia. The antinociception of spinal gabapentin is developed in injury-induced hyperalgesia without affecting acute nociception. The authors evaluated the effects of intrathecal gabapentin, NMDA antagonist (MK801) and AMPA antagonist (NBQX) in the formalin test which shows injury-induced hyperalgesia as well as acute pain. We further assessed the interactions between gabapentin and either MK801 or NBQX. Male Sprague-Dawley rats were implanted with intrathecal catheters. To evoke pain, 50 microliter of 5% formalin solution was injected into the hindpaw. The interaction was investigated by a fixed dose analysis or an isobolographic analysis. MK801 and NBQX suppressed flinching responses during phase 1 of the formalin test, while gabapentin had little effect on phase 1. All three agents decreased the phase 2 flinching response. A fixed dose analysis in phase 1 showed that gabapentin potentiated the antinociceptive effect of MK801 and NBQX. Isobolographic analysis in phase 2 revealed a synergistic interaction after coadministration of gabapentin-MK801 or gabapentin-NBQX. Correspondingly, spinal gabapentin with NMDA or AMPA antagonist may be useful in managing acute pain and injury-induced hyperalgesia.

Interaction between Intrathecal Gabapentin and Adenosine in the Formalin Test of Rats

Spinal gabapentin and adenosine have been known to display an antinociceptive effect. We evaluated the nature of the interaction between gabapentin and adenosine in formalin-induced nociception at the spinal level. Male Sprague-Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, 50 microliter) into the hindpaw. After examination of the effects of gabapentin and adenosine, the resulting interaction was investigated with isobolographic and fractional analyses. Neither gabapentin nor adenosine affected motor function. Gabapentin or adenosine decreased the sum of the number of flinches during phase 2, but not during phase 1 in the formalin test. Isobolographic analysis, in phase 2, revealed an additive interaction between gabapentin and adenosine. Taken together, intrathecal gabapentin and adenosine attenuated the facilitated state and interacted additively with each other.

Effect of the administration of gabaergic agonists of the GABA A/BDZ receptor on sleep in human subjects

El objetivo de este estudio ha sido evaluar los efectos de la administración aguda de una única dosis de una benzodiacepina de acción prolongada (diacepam, 10 mg), una imidazopiridina (zolpidem, 10 mg), una ciclopirrolona (zopiclona, 7.5 mg), un agonista del complejo molecular GABA A/BDZ (Gabob, 500 mg), y un placebo, sobre el sueño en diez sujetos sanos, utilizando un diseño doble-ciego de cuadrado latino de bloques incompletos. Para ello, se hizo un registro polisomnográfico nocturno (de ocho horas de duración) de cada sujeto durante seis noches consecutivas, en donde se evaluaban variables polisomnográficas relacionadas con la cantidad y la calidad de sueño. Nuestros resultados indicaron que no hubo ningún cambio significativo en las variables polisomnográficas relacionadas con la cantidad de sueño tras la administración de las sustancias. En cambio, los fármacos afectaron tres variables relacionadas con la calidad de sueño; en concreto, al porcentaje de la fase I de sueño, al de sueño; en concreto, al porcentaje de la fase I de sueño, al de sueño MOR (Movimientos Oculares Rápidos) y al de los episodios de la fase II. Por otra parte, nuestros resultados pusieron de manifiesto que la zopiclona fue la sustancia que produjo una mejoría significativa en las variables polisomnográficas relacionadas con la cantidad de sueño, cuando las comparaciones estadísticas se establecieron entre la línea base, la administración del fármaco y el periodo de levado del fármaco. No obstante, el placebo produjo un empeoramiento de las variables polisomnográficas relacionadas con la cantidad de sueño, evidenciándose un claro "efecto placebo" sobre las variables polisomnográficas

Effect of continuous infusion of GABA and baclofen on gastric secretion in anaesthetised rats.

Continuous infusion of gamma- aminobutyric acid (GABA) and baclofen (BAC) on gastric acid and pepsin secretion in perfused rat stomach showed that GABA (25-100 mg/kg/hr, i.v.) and BAC (1 mg/kg/hr, i.v.) increased the acid output which was blocked by bicuculline (Bicc, 1 mg/kg, i.v.) when given 30 min before their infusion. However, lower dose of GABA (5 mg/kg/hr) and hig her doses of BAC (5 or 10 mg/kg/hr) did not show any significant effect on acid secretion. GABA (5 and 25 mg/kg/hr) inhibited peptic output and again Bicc in the above dose inhibited the inhibitory effect of 25 mg/kg/hr of GABA on peptic output. The result indicate dichotomy on the effects of GABA on acid and pepsin secretion. As both the effects were blocked by Bicc, involvement of GABAA receptor may be a possibility. The antiulcer effect of GABA and BAC could not be due to their effect on gastric acid secretion, but may be due to inhibition of pepsin secretion by GABA or effects of GABA or BAC on mucosal defensive factors.

Effect of application of gamma amino butyric acid at the medial preoptic area on sleep-wakefulness.

Intracerebral microinjections of gamma amino butyric acid were given bilaterally at the medial preoptic area (mPOA) to determine the possible role of this neurotransmitter in the genesis and regulation of sleep-wakefulness. GABA (50 micrograms/0.2 microliters) when administered through chronically implanted cannulae in free moving rats, did not produce any significant alterations in sleep-wakefulness. This may be attributed either to the non-involvement of GABA at the level of mPOA in the regulation of sleep, or to other factors like the low dose and rapid breakdown of the injected drug.

Eficacia y seguridad del vigabatrin en tratamiento adicionado en pacientes con epilepsia parcial refractaria / Safety and efficacy studies of vigabatrin in combined treatment in patients with partial refractory epilepsy

Los estudios epidemiológicos realizados en las últimas décadas han demostrado que alrededor de las tres cuartas partes de los pacientes epilépticos pueden en la actualidad, ser controlados eficazmente con las drogas anticonvulsivantes. Sin embargo alrededor del 20 A 30 por ciento de los mismos, continúan presentando crisis a pesar de la instauración de un tratamiento farmacológico correcto. La reciente introducción de nuevas drogas, una de las cuales es el vigabatrin, podría constituir un paso adelante hacia el control de algunos de estos pacientes. Con el objetivo de determinar la eficacia y la tolerabilidad de esta droga en pacientes que no habían respondido a tratamientos farmacológicos previos, hemos realizado un estudio prospectivo en 20 pacientes con epilepsia parcial, refractaria al tratamiento farmacológico y por otra parte, hemos analizado el impacto de la misma a nivel del estado de la atención tanto en el plano de la conducta como su correlato electrofisiológico. El 65 por ciento de los pacientes presentó una disminución de más del 50 por ciento de las crisis. Se presentaron efectos adversos en el 35 por ciento de los pacientes. Los efectos adversos más importantes observados por nosotros fueron los efectos centrales. En el estudio de cuantificación de la actividad de base del EEG (qEEG) se observó una disminución de la potencia relativa en las bandas de frecuencia lentas y en aquellos pacientes que presentaron una reducción de las crisis superior al 50 por ciento , una mayor organización de la actividad eléctrica y una mejor ejecución de las pruebas de tiempo de reacción simple y atención selectiva

Changes in succinate dehydrogenase activity of rats after intraventricular injections of GABA, muscimol and picrotoxin.

Effects of intraventricular injections of GABA, and a GABA agonist, muscimol and an antagonist, picrotoxin on succinate dehydrogenase (SDH) enzyme activity in plasma and a few hypothalamic nuclei of brain of rats have been investigated using biochemical, histochemical and cytophotometric techniques. Results show that SDH decreased by GABA and muscimol treatment, and increased after picrotoxin injection. From the above findings, it is apparent that GABA, muscimol and picrotoxin influence SDH activity of plasma and hypothalamic nuclei.

Effect of GABA, muscimol and picrotoxin given in third ventricle on serum cholinesterases and monoamine oxidase and on plasma succinic dehydrogenase in rats.

Effect of injection in third ventricle of GABA, the GABA agonist muscimol, and the GABA antagonist picrotoxin on the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and monoamine oxidase (MAO) in serum and succinic dehydrogenase (SDH) in plasma has been studied. Surprisingly, the AChE, BuChE, MAO and SDH enzymes activity were inhibited by GABA and muscimol, while they were enhanced by picrotoxin.