Montelukast reduces seizures in pentylenetetrazol-kindled mice

Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Montelukast (10 mg/kg, sc) and phenobarbital (20 mg/kg, sc) increased the latency to generalized seizures in kindled mice. Montelukast increased CysLT1 immunoreactivity only in non-kindled, PTZ-challenged mice. Interestingly, PTZ challenge decreased CysLT2 immunoreactivity only in kindled mice. CysLT1 antagonists appear to emerge as a promising adjunctive treatment for refractory seizures. Nevertheless, additional studies are necessary to evaluate the clinical implications of this research.

FTIR microspectroscopy reveals chemical changes in mice fetus following phenobarbital administration

Phenobarbital is a phenobarbiturate used as a sedative, anticonvulsant or hypnotic with the doses prescribed and can cause teratogenic effects. The goal of this study was to examine an alternative method for the recognition of the mechanism or the bimolecular potential changes in mice fetus caused by Phenobarbital using FTIR micro spectroscopy. The mice were injected with Phenobarbital [120 mg/Kg] on gestation day 9. Fetuses were dissected on day 15 of gestation and morphological and histological studies on the fetus were carried out. Sections [10 microm] of normal and Phenobarbital treated fetus brains and livers were used for FTIR measurement in the wave number region of 400- 4000 cm. The results were shown by 2 derivatization of spectra and also subtracting from control spectra. In liver, the intensity at 1054 cm, 1155 cm, 1353 cm, 1453cm,1645 cm, 1622 cm, 2944 cm, 2913 cm and 2845 cm were shifted and increased. In the brain, the intensity at 879 cm, 911 cm, 955 cm, 1223 cm, 1256 cm, 1304 cm, 1360 cm, 1453 cm, 1529 cm, 1636 cm, 2845 cm, 2915 cm and 2950 cm were increased and shifted. The most important changes of the fetus brain tissue are on the beta structure of proteins due to the amide I bands at 1636 cm, while extensive effects on the DNA structure were obvious for the Phenobarbital treated liver tissues. As a conclusion, FTIR spectroscopy might well be assumed as a potentially powerful teratogenic measurement instrument with a unique ability to identify the modified bimolecular structures

Esquizencefalia de labio cerrado bilateral: a propósito de un caso / Schizencephaly of bilateral closed lip: speaking of one case

La esquizencefalia es un desorden de la migración neuronal, caracterizada por hendiduras de sustancia gris en los hemisferios cerebrales que se extienden desde la superficie pial a los ventrículos laterales. Esta patología es el resultado final de una amplia variedad de factores genéticos, tóxicos, metabólicos y de agentes infecciosos que ocurren durante un período crítico del desarrollo cerebral. Esta malformación puede ser unilateral o bilateral y puede ser dividida en dos subtipos: de ¨labios cerredos" o tipo I, o de "Labios abierto" o tipo II. Presentamos el caso de una paciente demenina de 37 años de edad con epilepsia y hallazgos neurorradiológicos de esquizencefalia de "labios cerrados" bilateral

Schizencephaly is a rare developmental of neuronal migration, characterized by congenital clefts spanning the cerebral hemisphere from the pial surface to the lateral ventricle and lined by cortical gray matter. The lesion is the final result of a variety of etiologies including genetic, toxic, metabolic and infectious agents during a critical period of the development of the brain. This malformation can be unilateral or bilateral and may be divided in two subtypes: "closed tips" or type I and "open tips" or type II. We present 37 years old female patient with epilepsy and neuroradiological findings of bilateral "closed lips" schizencephaly

effect of anticonvulsant drugs [phenobarbital and valproic acid] on the serum level of cholesterol, triglyceride, lipoprotein and liver enzymes in convulsive children

Studies on the effect of various antiepileptic drugs on serum lipids show contradictory results. We aimed to find the effect of Phenobarbital and Sodium Valproate monotherapy on serum lipid profile and liver function tests in epileptic children. This cohort study was concducted in Amirkola Children Hospital. One hundred and ten children with epilepsy were included in this study. Children with hepatic or renal disease, those receiving medications which could alter liver function tests or serum lipid profile were excluded from the study. Patients were allocated into two groups. The first group, including 63 patients, received Phenobarbital and the second group, including 47 patients, received Sodium Valproate, both in divided doses. A venous blood sample was collected after overnight fasting to evaluate serum triglyceride, total cholesterol, LDL, HDL, and liver function tests. Data was analyzed with SPSS version 27. In children receiving Phenobarbital, total cholesterol, LDL, HDL, ALP, SGOT and SGPT increased significantly after treatment, but TG level showed no significant changes. In children receiving Sodium Valproate, HDL, ALP, SGOT, SGPT significantly increased after treatment but there were no statistically significant changes in total cholesterol, LDL and TG. In our study, the plasma levels of LPa elevated significantly after treatment with Phenobarbital and Sodium Valproate [P Value=0.0001]. This increase was more significant in patients receiving Sodium Valproate. Our results suggested a need for monitoring serum total cholesterol, HDL, LDL,and TG levels in patients receiving Phenobarbital and Valproic Acid

Hepatoprotective activity of six polyherbal formulations in CCl4-induced liver toxicity in mice.

To evaluate pretreatment of six polyherbal liquid formulations (PLFs) commercially available in India, on CCl4-induced liver injury, Swiss albino mice were treated for 7 days with distilled water or PLFs (2.6 and 5.2 ml/kg body weight/day, po) followed by single sc injection of 50% (v/v) CCl4 in arachis oil at a dose of 1 ml/kg. The serum biochemical parameters such as alanine transaminases, aspartate transaminases and alkaline phosphatase were estimated. Phenobarbitone-induced sleeping time and liver histopathology were also carried out. CCl4-treated animals showed significant increase in the levels of liver enzymes, phenobarbitone-induced sleeping time and revealed fatty changes and centrizonal necrosis on histological examination of liver indicating hepatic damage. When pretreated with PLFs at a dose of 5.2 ml/kg body weight/day, the CCl4-induced changes were significantly reversed. The pretreatment with PLFs can prevent acute liver damage induced by CCl4 only at a higher dose. Therefore, it is suggested that a dose adjustment of these PLFs may be necessary for their optimal effects in human liver diseases.

Phenobarbital influence on neuromuscular block produced by rocuronium in rats / Influência do fenobarbital no bloqueio neuromuscular produzido pelo rocurônio em ratos

PURPOSE: To evaluate in vitro and in vivo neuromuscular blockade produced by rocuronium in rats treated with Phenobarbital and to determine cytochrome P450 and cytochrome b5 concentrations in hepatic microsomes. METHODS: Thirty rats were included in the study and distributed into 6 groups of 5 animals each. Rats were treated for seven days with phenobarbital (20 mg/kg) and the following parameters were evaluated: 1) the amplitude of muscle response in the preparation of rats exposed to phenobarbital; 2) rocuronium effect on rat preparation exposed or not to phenobarbital; 3) concentrations of cytochrome P450 and cytochrome b5 in hepatic microsomes isolated from rats exposed or not to phenobarbital. The concentration and dose of rocuronium used in vitro and in vivo experiments were 4 µg/mL and 0,6 mg/kg, respectively. RESULTS: Phenobarbital in vitro and in vivo did not alter the amplitude of muscle response. The neuromuscular blockade in vitro produced by rocuronium was significantly different (p=0.019) between exposed (20 percent) and not exposed (60 percent) rats; the blockade in vivo was significantly greater (p=0.0081) in treated rats (93.4 percent). The enzymatic concentrations were significantly greater in rats exposed to phenobarbital. CONCLUSIONS: Phenobarbital alone did not compromise neuromuscular transmission. It produced enzymatic induction, and neuromuscular blockade in vivo produced by rocuronium was potentiated by phenobarbital.

OBJETIVO: Avaliar in vitro e in vivo o bloqueio neuromuscular produzido pelo rocurônio em ratos tratados com fenobarbital e determinar as concentrações de citocromo P450 e b5 em microssomos hepáticos. MÉTODOS: Trinta ratos foram incluídos no estudo e distribuídos em seis grupos de cinco animais cada. Ratos foram tratados por sete dias com fenobarbital (20 mg/kg) e avaliou-se: 1) amplitude das respostas musculares em preparação de ratos expostos ao fenobarbital; 2) o efeito do rocurônio em preparações de ratos expostos ou não ao fenobarbital; 3) as concentrações de citocromo P450 e b5 em microssomos isolados de fígados dos ratos expostos ou não ao fenobarbital. A concentração e dose de rocurônio utilizadas nos experimentos in vitro e in vivo foram respectivamente de 4 µg/mL e 0,6 mg/kg. RESULTADOS: In vitro e in vivo, o fenobarbital não alterou a amplitude das respostas musculares. In vitro, o bloqueio produzido pelo rocurônio foi significativamente diferente (p=0.019) entre expostos (20 por cento) e não expostos (60 por cento); in vivo o bloqueio foi significativamente maior (p=0.0081) nos ratos tratados (93,4 por cento). As concentrações enzimáticas foram significativamente maiores nos ratos expostos ao fenobarbital. CONCLUSÕES: O fenobarbital isoladamente não comprometeu a transmissão neuromuscular. Ocasionou indução enzimática, e in vivo o bloqueio com o rocurônio foi potencializado pelo fenobarbital.

Prenatal Diagnosis of Fetal Seizure: A Case Report

A 35-yr-old woman carrying a 17-week-old fetus presented with right hydronephrosis and a single umbilical artery. Karyotyping was normal and targeted ultrasonography showed an otherwise normal fetus. After 28 weeks of gestation, the mother felt rapid, repetitive fetal movement and an ultrasound at 30 weeks of gestation revealed tonic clonic movements of the fetal trunk and extremities. At 36 weeks of gestation, an emergency repeat Cesarean section was performed because of a premature rupture of the membranes and a male infant weighing 4,295 gm was delivered. After birth, the infant continued to have movements suggestive of a generalized tonic clonic seizure. Brain computed tomography and magnetic resonance imaging revealed normal structures and an electroencephalography showed generalized suppression. Treatment with phenobarbital resulted in substantial improvement in the number of seizure episodes, however fine seizure-like movement continued in both of the hands, feet and in the tongue until the five-month follow-up. This is the first Korean report of a fetal seizure being diagnosed during the prenatal period.

Modelo experimental de indução de lesão oxidativa hepática em ratos por halotano / Experimental model of liver oxidative damage induction in rats by halothane

RACIONAL: O anestésico halotano pode ser metabolizado redutivamente a intermediários reativos que podem iniciar a lipoperoxidação acompanhada de injúria hepática. O tratamento prévio com hipóxia e fenobarbital em ratos aumenta o metabolismo do halotano e o estresse oxidativo e causa mudanças nas enzimas antioxidantes no fígado com dano hepático. MÉTODOS: Investigou-se o efeito do halotano na lipoperoxidação e histologia hepáticas após o aumento do metabolismo redutor do halotano induzido pela hipóxia e fenobarbital. Vinte e cinco ratos machos Wistar foram divididos em cinco grupos: Co (controle), HO14 (Halotano/Hipóxia), F (Fenobarbital), O14 (Hipóxia) e H (Halotano). Após 24 horas os ratos foram sacrificados, seus fígados foram retirados para determinar quimiluminescência, substâncias que reagem ao ácido tiobarbitúrico, enzimas antioxidantes, superóxido dismutase, catalase e amostras de sangue foram tomadas para determinar AST e a ALT. A avaliação histopatológica foi realizada pela técnica de hematoxilina-eosina. Os dados da avaliação histológica foram apresentados através de mediana e amplitude entre quartis. RESULTADOS E CONCLUSÕES: A exposição ao halotano/hipóxia causou lipoperoxidação hepática e mudanças significativas na atividade das enzimas antioxidantes. Além disso, provocou lesão histopatológica do fígado e aumento significativo dos níveis plasmáticos de AST e ALT.

BACKGROUND: The anesthetic halothane can be reductively metabolized to reactives intermediates that may initiate lipid peroxidation accompanied by hepatic injury. Hypoxia and phenobarbital pretreatment in rats increases metabolism of halothane, the oxidative stress, cause liver antioxidant enzymes changes and tissue damage. AIMS: We investigated the effect of halothane on hepatic lipid peroxidation and on hepatic histology after increases reductive metabolism of halothane caused by hypoxia and phenobarbital pretreatment. METHODS: Twenty-five male wistar rats were divided in five equals groups: CO (Control), HO14 (Halothane/Hypoxia), F (fenobarbital alone), O14 (Hypoxia alone) and H (Halothane alone). After 24 hours the rats were killed, their livers removed to determine chemoluminescence, thiobarbituric acid-reactive substances, catalase, superoxide dismutase, and blood samples were taken to determine AST and ALT. The histopathologic evaluation was performed with hematoxylin and eosin staining. Histopathologic scores are presented as 25th-75th percentile/range values and median ± range. RESULTS/CONCLUSION: Halothane-hypoxic exposure resulted in a significant changes in the activities of antioxidant enzymes, and induced hepatic lipoperoxidation. Moreover it resulted in histopathologic liver injury as well as significant increase of serum activity of AST and ALT.

[Comparing the effect of valproate and phenobarbital on weight gaining of epileptic children]

Respecting the high incidence of epilepsy among children and several reports coresponding the weight gaining of some during the valproate therapy, this study was conducted in "Mofid Children's Hospital" during 1384 to determine and compare the occurrence and severity of weigh gain among children treated with either valproate or phenobarbital. This clinical trails study was performed studying on 60 epileptic patients. We applied "International League against Epilepsy" classification to diagnose the patients. They were randomly equally divided into two groups [random allocation]. First group was treated with valproate 20 mg/kg/day, whereas second one received Phenobarbital 5 mg/kg/day [in divided dose]. Patients were followed for a six-month period. Body mass index [BMI] was measured at first, 2[nd], 4[th] and 6[th] months of therapy and BMI[6] was compared with expected BMI[6] [according to BMI curve] and the difference of latter two BMIs [BMI[6] and expected BMI[6]] were calculated. McNemar's test was used to compare the weight difference in each group and Chi-square test was applied for between-groups comparison. In valproate-treated patients whose their weights increased, some characteristics [including age, sex and primary weight] were evaluated by Fisher's exact test. Two groups were identical with respect to their age, sex, primary BMI and weight. 4 patients of phenobarbital group [13.3%] versus 20 patients of valproate group [66.7%], had weight gain [P=0.6 and P<0.0001, respectively]. Final-stage data revealed that compared to phenobarbital, valproate resulted in further weight gaining of children and adolescent [P<0.001]. Moreover, in valproate treated group, patients with older age and higher BMI, were more at risk of gaining weight. The risk of weight gainning in epileptic children treated with valproate is high. It seems that in patients above 10 years old and fat patients, this risk become more. We recommend further study to evaluate the effect of valproate on weight of epileptic patients older than 10 years and also fat patients

A relação do uso crônico de fenobarbital com áreas potencialmente pré-neoplásicas em fígado de ratos / Potentially pre-neoplasics areas in rat's liver associated to chronic use of phenobarbital

RACIONAL: O fenobarbital é utilizado em modelos experimentais não só por ser um importante agente promotor da carcinogênese em fígado de ratos, como também por ser não-genotóxico, órgão-específico e dose-dependente. OBJETIVOS: Avaliar o efeito da administração diária de fenobarbital em ratos, desde o nascimento até os 24 meses de idade, na ausência concomitante de administração de agentes químicos iniciadores da carcinogênese. MATERIAL E MÉTODOS: Um grupo controle de ratos machos Wistar recebeu dieta básica e a esta, do outro grupo, foi adicionado diariamente, fenobarbital a 0,05 por cento, durante 24 meses. Cortes dos lobos médio e direito do fígado foram submetidos ao processamento histológico e corados pela hematoxilina-eosina e coloração imunoistoquímica para a glutationa S-transferase forma placentária. RESULTADOS: Detectaram-se áreas glutationa S-transferase forma placentária positivas em ambos os grupos e as imagens foram analisadas quanto ao número e à extensão da superfície, mediante análise de imagem por histomorfometria. CONCLUSÃO: O uso crônico de fenobarbital não alterou o número de áreas glutationa S-transferase forma placentária positivas, havendo, no entanto, aumento no tamanho médio de áreas glutationa S-transferase forma placentária positivas, com conseqüente aumento da superfície glutationa S-transferase forma placentária positiva, sendo este aumento provavelmente relacionado a maior capacidade evolutiva dessas lesões e possível irreversibilidade das mesmas.

BACKGROUND: Phenobarbital has been used in experimental models because it is an important agent of carcinogenesis promotion in the liver of rats, and it is also non-genotoxic, organ-specific and dose-dependent. AIM: To evaluate the effects of the daily administration of phenobarbital in old rats treated with phenobarbital since their birth up to 24 months of age, in the absence of concomitant administration of chemical agents, which initiate carcinogenesis. PATIENTS AND METHODS: A control group of male Wistar rats was fed with a basic diet and a second group was fed with the same basic diet added of 0.05 percent of phenobarbital, for a period of 24 months. Medium and right liver fragments were submitted to the histological processing and they were stained by hematoxiciline and eosin and were immunohystochemically colored to glutathione S-transferase placentary form. RESULTS: Glutathione S-transferase placentary positive zones were detected in both groups and the images were analyzed concerning their number and surface extension through the technique of histometry analyses. CONCLUSION: Chronic use of phenobarbital did not modify the number of glutathione S-transferase placentary form positive areas. Although, data indicates that glutathione S-transferase placentary form positive areas media size are increased, probably because there are an increase in their evolution capacity and irreversibility.

Comparative evaluation of phenobarbital-induced CYP3A and CYP2H1 gene expression by quantitative RT-PCR in Bantam, Bantamized White Leghorn and White Leghorn chicks

The present work was to study induction of cytochrome P450 (CYP)3A and CYP2H1 gene by reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative RTPCR in Bantam, Bantamized White Leghorn and White Leghorn chicks. Out of 18 chicks total 3 from each group (Bantam, Bantamized White Leghorn and White Leghorn) were treated intraperitoneal with phenobarbital at the dose rate of 12 mg/100 g (body weight) while the control group was treated with the saline. Total RNA was extracted from the liver samples using Tri Reagent based method. First strand cDNA was synthesized using one step RT-PCR kit. The PCR was performed and the product was subjected to agarose gel electrophoresis. Quantitative RT-PCR was conducted to quantify gene expression level of CYP3A and CYP2H1 genes. Relative expression ratio of CYP3A and CYP2H1 genes was calculated using relative expression software tool (REST). It was found that CYP3A is up regulated by factor of 1.34, 14.51 and 1.00 in Bantam, Bantamized White Leghorn and White Leghorn chicks, respectively. In Bantam and Bantamized White Leghorn chicks CYP2H1 gene was up regulated by factor 1.50 and 80.87, respectively but down regulated by a factor of 1.97 in White Leghorn chicks. The PCR efficiency ranged from 1.30 to 1.70, 0.86 to 1.70 and 0.91 to 1.58 for CYP3A, CYP2H1 and beta-actin, respectively in Bantam, Bantamized White Leghorn and White Leghorn chicks.

The effect of L-arginine on the memory impairing action of phenobarbitone in rats that convulsed after the injection of picrotoxin.

Nitric oxide (NO) has been demonstrated to enhance memory formation in experimental animals. However, the effect of NO precursor, L-arginine has never been tested on the memory impairing action of the aniepileptic drug, phenobarbitone independently and concurrently with the convulsant, picrotoxin (PCT). In view of this, in the present study, rats that acquired the shock avoidance task were treated with PCT (5 mg/ kg). Twenty four h later these animals were injected with L-arginine (500, 1000 mg/kg) and phenobarbitone (10, 20 mg/kg). Retention of the acquired task was tested 30 min later. The effect of these compounds were correlated with the changes produced by them on the concentration of NO in the brain. PCT and phenobarbitone (20 mg/kg) inhibited memory process independently and concurrently. NO concentration was not altered by phenobarbitone but was decreased in PCT-treated animals. L-arginine (1000 mg/kg) increased the concentration of NO in PCT and phenobarbitone treated animals and prevented these compounds from impairing memory process independently and concurrently. These results lead to a conclusion that L-arginine may be used in combination with phenobarbitone to prevent both the cognitive side effect of the antiepileptic drug and the impairment of memory that is associated with the convulsion disorder.

Effect of undernutrition on morphine analgesia, haloperidol catalepsy and pentobarbitone sodium hypnosis in developing new born rats.

In the present study, half of the pups of a litter were undernourished by 12 h daily maternal deprivation from day 5 to day 18 postnatal and were subsequently nutritionally rehabilitated. Responses of CNS-acting drugs (morphine analgesia, pentobarbitone sodium hypnosis, haloperidol catalepsy) were studied at the age of day 9, 12 and 18 in maternally deprived and of day 25 in nutritionally rehabilitated new born rats as compared to that of their nourished littermates. The results showed that the response of these CNS-acting drugs was maximum at the age of day 9 postnatal and progressively decreased thereafter as the age of the animal advanced. The responses of these drugs in maternally deprived animals varied on different days of undernourishment as compared to that of their nourished littermates. The responses were significantly less in first half and were significantly more in second half period of undernourishment. The changes observed in the responses of these CNS-acting drugs were directly related to the changes observed in brain serotonin level in maternally deprived and nutritionally rehabilitated new born rats. The present findings suggest that the nature and degree of undernutrition imposed in suckling rats might only produce temporary effects on the response of CNS-actin drugs and on brain serotonin levels which is reversible if undernourished new born rats were nutritionally rehabilitated on an appropriate time of brain development.

Effect of prenatal diazepam, phenobarbital, haloperidol and fluoxetine exposure on foot shock induced aggression in rats.

Different groups of pregnant rats were treated with diazepam (10 mg/kg), phenobarbital (10 mg/kg), haloperidol (0.1 mg/kg), fluoxetine (10 mg/kg) and vehicle (normal saline) intraperitoneally once a day during gestation days 13 to 21. After birth these pups were culled to 8 pups/dam and foster-nursed by lactating mothers for 3 weeks and were reared in colony cages thereafter. Sex and weight matched pairs of rat offsprings were subjected to foot shock induced aggression test at 8 weeks of age. Two parameters of aggressive behaviour were recorded namely, the latency to fight and total number of fighting bouts. The results indicate that prenatal exposure to diazepam, phenobarbital, haloperidol and fluoxetine caused significantly enhanced aggression in terms of number of fighting bouts.

Combined anticonvulsant activity of verapamil and phenobarbitone in mice

This study aimed to investigate the anticonvulsant activity of different combinations of phenobarbitone and verapamil. The effect of intraperitoneal[ip] administration of verapamil into mice in a dose of 10 mg/kg on the anticonvulsant activity of phenobarbitone [PB] injected ip in doses of 10, 20, 30 and 40 kg/mg was investigated. Verapamil was allowed to act for five minutes and phenobarbitone for thirty minutes prior to injection of the convulsive agents. Verapamil was given either alone or in combination with different doses of phenobarbitone. Convulsions were induced in animals by pentylenetetrazole [PTZ] in a dose of 100 mg/kg or by strychnine in a dose of 1 mg/kg

Influence of the combined administration of verapamil and phenobarbitone on brain and serum electrolytes in mice

This study was conducted to investigate the mechanism of action of phenobarbitone and verapamil and their concurrent use as anticonvulsant agents against chemically-induced seizures. Brain and serum Na+, Ca2+, K+ ions were measured in different groups of mice; those receiving saline [control] and others receiving the convulsive agent pentylenetetrazole in a dose of 100 mg/kg or strychnine in a dose of 1 mg/kg. In addition, brain and serum electrolytes were measured in mice treated with verapamil in a dose of 10 mg/kg and different doses of phenobarbitone in a doses of 10, 20, 30 and 40 mg/kg] as well as various combination of one dose level of verapamil with the four selected dose levels of phenobarbitone. The results revealed that the ip administration of phenobarbitone in its selected four dose levels was able to significantly and dose-dependently lower the brain calcium level. Moreover, the co-administration of phenobarbitone in its four dose levels with the fixed dose of verapamil [10 mg/kg] was found to bring about lowering of the brain calcium content in all groups of mice treated with the various verapamil- phenobarbitone combinations

Partial recovery of erythrocyte glycogen in diabetic rats treated with phenobarbital

Erythorocytes may play a role in glucose homeostasis during the postprandial period. Erythrocytes from diabetic patients are defective in glucose transport and metabolism, functions that may affect glycogen storage. Phenobarbital, a hepatic enzyme inducer, has been used in the treatment of patients with non-insulin-dependent diabetes mellitus (NIDDM), increasing the insulin-mediated glucose disposal. We studied the effects of phenobarbital treatment in vivo on glycemia and erythrocyte glycogen content in control and alloxan-diabetic rats during the postprandial period. In control rats (blood glucose, 73 to 111 mg/dl in femoral and suprahepatic veins) the erythrocyte glycogens content was 45.4 + 1.1 and 39.1 + 0.8 mug/g Hb (mean + SEM, N = 4-6) in the femoral artery and vein, respectively, and 37.9 +1.1 in the portal vein and 47.5 + 0.9 in the suprahepatic vein. Diabetic rats (blood glucose 300-350 mg/dl) presented low (p<0.05) erythrocyte glycogen content, i.e., 9.6 + 0.1 and 7.1 + 0.7 mug/g Hb in the femoral artery and vein, respectively, and 10.0 + 0.7 and 10.7 + 0.5 in the portal and suprahepatic veins, respectively. After 10 days of tratment, phenobarbital (0.5 mg/ml in the drinking water) did not change blood glucose or erythrocyte glycogen content in control rats. In diabetic rats, however, it lowered (P<0.05) blood glucose in the femoral artery (from 305 + 18 to 204 + 45 mg/dl) and femoral vein (from 300 + 11 to 174 + 48 mg/dl) and suprahepatic vein (from 350 + 10 to 174 + 42 mg/dl), but the reduction was not sufficient for complete recovery. Phenobarbital also stimulated the glycogens synthesis, leading to a partial recovery of glycogen stores in erythrocytes. In treated rats, erythrocyte glycogen content increased to 20.7 + 3.8 mug/g Hb in the femoral artery and 30.9 + 0.9 mug/g Hb in the suprahepatic veins (p<0.05). These data indicate that phenobarbital activated some of the insulin-stimulated glucose matabolism steps which were depressed in diabetic srythrocytes, supporting the view that erythrocytes participate in glucose homeostasis.

Terapêutica em epilepsia / Therapeutics in epilepsy

Esta revisão sumária sobre terapêutica em epilepsia aborda questões tais como quando começar o tratamento, qual a droga antiepilética (DAE) indicada para os diversos tipos de crise, quando retirar a DAE, sua posologia, frequência de tomadas, efeitos colaterais e idução/inibição enzimática da DAE, monitorização do tratamento e epilepsia refratária. Várias dessas questões são dependentes do conhecimento de farmacocinética e farmacodinâmica, fatos que também são considerados.

Hyperalgesic effect induced by barbiturates, midazolam and ethanol: pharmacological evidence for GABA-A receptor involvement

The involvement of GABA-A receptors in the control of nociception was studied using the tail-flick test in rats. Non-hypnotic doses of the barbiturates phenobarbital (5-50 mg/kg), pentobarbital (17-33 mg/kg), and thiopental (7.5-30 mg/kg), of the benzodiazepine midazolam (10 mg/kg) or of ethanol (0.4-1.6 g/kg) administered by the systemic route reduced the latency for the tail-flick response, thus inducing a 'hyperalgesic' state in the animals. In contrast, non-convulsant doses of the GABA-A antagonist picrotoxin (0.12- 1.0 mg/kg) administered systemically induced an increase in the latency for the tail-flick response, therefore characterizing an 'antinociceptive' state. Previous picrotoxin (0.12 mg/kg) treatment abolished the hyperalgesic state induced by effective doses of the barbiturates, midazolam or ethanol. Since phenobarbital, midazolam and ethanol reproduced the described hyperalgesic effect of GABA-A-specific agonists (muscimol, THIP), which is specifically antagonized by the GABA-A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically involved in the modulation of nociception in the rat central nervous system.