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Anticonvulsant Drugs (anticonvulsant + drug)
Selected AbstractsEffects of lamotrigine in patients with bipolar disorder and alcohol dependenceBIPOLAR DISORDERS, Issue 3 2006Gabriel Rubio Background:, Bipolar disorder is significantly associated with alcohol use disorders. Anticonvulsant drugs are used in the treatment of bipolar disorder and they have also been used to treat alcohol dependence. The purpose of the present study was to evaluate tolerance and safety of lamotrigine in a dual-diagnosis population presenting bipolar disorder and alcohol dependence. Open-label lamotrigine was examined in 28 outpatients with DSM-IV bipolar disorder and alcohol dependence. Lamotrigine was added to existing medication regimens. Method:, Lamotrigine was started at a dose of 25 mg/day and titrated to a maximum dose of 300 mg/day. Subjects received a baseline evaluation which included a Structured Clinical Interview for DSM-IV (SCID) and weekly assessments for 12 weeks with the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), Severity of Alcohol Dependence Scale (SADS), a Visual Analogue Scale for Craving severity (VASC), and alcohol consumption. The concentration of carbohydrate-deficient transferrin (CDT) was used as an indirect measure of alcohol consumption. The sample consisted of 18 men and 10 women diagnosed with alcohol dependence and bipolar disorder I (n = 21) or bipolar disorder II (n = 7), with a mean age of 36.5 ± 7.7 years. Results:, Significant improvement was observed in HAM-D, YMRS, and BPRS scores (p < 0.01). Craving and CDT also significantly decreased (p < 0.001). Lamotrigine was well tolerated with no dropout subjects due to adverse events. Conclusion:, Lamotrigine is safe and well tolerated in this sample and associated with improvement in mood, alcohol craving and alcohol consumption. A placebo-controlled study would be of interest. [source] Anticonvulsant Profile and Teratogenicity of N -methyl-tetramethylcyclopropyl Carboxamide: A New Antiepileptic DrugEPILEPSIA, Issue 2 2002Nina Isoherranen Summary: ,Purpose: The studies presented here represent our efforts to investigate the anticonvulsant activity of N -methyl-tetramethylcyclopropyl carboxamide (M-TMCD) and its metabolite tetramethylcyclopropyl carboxamide (TMCD) in various animal (rodent) models of human epilepsy, and to evaluate their ability to induce neural tube defects (NTDs) and neurotoxicity. Methods: The anticonvulsant activity of M-TMCD and TMCD was determined after intraperitoneal (i.p.) administration to CF#1 mice, and either oral or i.p. administration to Sprague,Dawley rats. The ability of M-TMCD and TMCD to block electrical-, chemical-, or sensory-induced seizures was examined in eight animal models of epilepsy. The plasma and brain concentrations of M-TMCD and TMCD were determined in the CF#1 mice after i.p. administration. The induction of NTDs by M-TMCD and TMCD was evaluated after a single i.p. administration at day 8.5 of gestation in a highly inbred mouse strain (SWV) that is susceptible to valproic acid,induced neural tube defects. Results: In mice, M-TMCD afforded protection against maximal electroshock (MES)-induced, pentylenetetrazol (Metrazol)-induced, and bicuculline-induced seizures, as well as against 6-Hz "psychomotor" seizures and sound-induced seizures with ED50 values of 99, 39, 81, 51, and 10 mg/kg, respectively. In rats, M-TMCD effectively prevented MES- and Metrazol-induced seizures and secondarily generalized seizures in hippocampal kindled rats (ED50 values of 82, 45, and 39 mg/kg, respectively). Unlike M-TMCD, TMCD was active only against Metrazol-induced seizures in mice and rats (ED50 values of 57 and 52 mg/kg, respectively). Neither M-TMCD nor TMCD was found to induce NTDs in SWV mice. Conclusions: The results obtained in this study show that M-TMCD is a broad-spectrum anticonvulsant drug that does not induce NTDs and support additional studies to evaluate its full therapeutic potential. [source] Veterinarians' preferences for anticonvulsant drugs for treating seizure disorders in dogs and catsAUSTRALIAN VETERINARY JOURNAL, Issue 11 2009EK Kluger Objective To identify veterinarians' approaches and concerns when managing canine and feline patients with acute and chronic seizure disorders. Design Cross-sectional survey. Method A questionnaire was distributed to veterinarians to determine how many dogs and cats they were actively treating for seizures, their anticonvulsant drug (ACD) preferences for treating acute and chronic seizure disorders and whether serum anticonvulsant concentrations and/or biochemical analytes were routinely measured. Additional questions involved the respondent's year and place of graduation and identified concerns they faced when managing patients with seizure disorders. Results Phenobarbitone was the most commonly used ACD for managing chronic seizure disorders in both dogs and cats, with 82% of respondents using a combination of phenobarbitone and potassium bromide to manage refractory seizure disorders in dogs. Most respondents (96%) felt comfortable managing seizures in dogs, but only 63% were comfortable managing affected cats. Routine monitoring of serum ACD concentrations and of liver biochemical analytes was performed routinely by 71% and 45% of respondents, respectively. Of the respondents, 86% graduated from Australian universities and of these 53% had graduated after 1985. Conclusion Veterinarians identified when to commence medication, whether regular monitoring of serum ACD concentrations and liver enzyme activity was necessary, and if the cost was justified. Veterinarians also identified the need to balance dose rates and side-effects by using combination therapy, and the importance of providing accurate information to clients about what to expect in terms of seizure control for their pet. [source] Impurities,The hidden danger in anticonvulsant drugsEPILEPSIA, Issue 1 2008Thomas Peter Sabroe No abstract is available for this article. [source] Riluzole inhibits the persistent sodium current in mammalian CNS neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2000Andrea Urbani Abstract The effects of 0.1,100 ,m riluzole, a neuroprotective agent with anticonvulsant properties, were studied on neurons from rat brain cortex. Patch-clamp whole-cell recordings in voltage-clamp mode were performed on thin slices to examine the effects of the drug on a noninactivating (persistent) Na+ current (INa,p). INa,p was selected because it enhances neuronal excitability near firing threshold, which makes it a potential target for anticonvulsant drugs. When added to the external solution, riluzole dose-dependently inhibited INa,p up to a complete blocking of the current (EC50 2 ,m), showing a significant effect at therapeutic drug concentrations. A comparative dose-effect study was carried out in the same cells for the other main known action of riluzole, the inhibitory effect on the fast transient sodium current. This effect was confirmed in our experiments, but we found that it was achieved at levels much higher than putative therapeutic concentrations. Only the effect on INa,p, and not that on fast sodium current, can account for the reduction in neuronal excitability observed in cortical neurons following riluzole treatment at therapeutic concentrations, and this might represent a novel mechanism accounting for the anticonvulsant and neuroprotective properties of riluzole. [source] An improved brain slice model of nerve agent-induced seizure activityJOURNAL OF APPLIED TOXICOLOGY, Issue S1 2001Sebastien J. Wood Abstract A brain slice model was developed to investigate the mechanisms of seizure activity induced by soman and the effectiveness of potential anticonvulsant drugs. Unlike previously reported slice studies with nerve agents, this model contains the entorhinal cortex as well as the hippocampus. This allows the study of the spread of seizure discharges within the limbic system and the development of prolonged, sustained discharges that are rarely seen in the simple hippocampal slice preparation. Soman (1 µM) induced a second population spike in the evoked field potential in the CA1 or CA3 region within 15,20 min. In almost all the slices tested, this developed into spontaneous seizure activity within 30,40 min. As well as interictal bursts, many slices also showed longer periods of high-frequency bursting analogous to ictal seizure activity that originated in the entorhinal cortex. This activity appeared similar to that induced by the muscarinic agonist pilocarpine. Both the second population spike and the spontaneous discharges could be blocked by diazepam and by AMPA/kainate antagonists, but not by the NMDA antagonists AP5 and MK-801. This study confirms that the combined hippocampal,entorhinal cortex slice preparation is a suitable model for investigating the origin and propagation of nerve-agent-induced seizures within the limbic system. Copyright © 2001 John Wiley & Sons, Ltd. [source] Global physicochemical properties as activity discriminants for the mGluR1 subtype of metabotropic glutamate receptorsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 16 2001Marta Filizola Abstract Metabotropic glutamate receptors (mGluRs) are important as candidate therapeutic targets for many neurological disorders. In the present work, the focus has been on the mGluR1 subtype, where agonists have a proconvulsant profile while antagonists exert anticonvulsant activity. Identification of molecular determinants for the inhibition of mGluR1 provides a new avenue for the discovery and development of novel anticonvulsant drugs. Spatial configuration of key groups alone cannot explain activation selectivity at this specific receptor subtype. In fact, all known agonists and antagonists acting at mGluR1 can accommodate the same critical moieties in a similar geometric arrangement that corresponds to the extended conformation of glutamate. Therefore, other factors must account for the differences in activation. This study presents the results of an analysis of a large suite of steric, topological, electrostatic, and thermodynamic molecular properties calculated for a representative set of potent mGluR1 agonists and antagonists. Global steric parameters and the total nonpolar area provide discrimination between the mGluR1 agonists and antagonists considered in the present work. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 2018,2027, 2001 [source] Effects of some synthetic kynurenines on brain amino acids and nitric oxide after pentylenetetrazole administration to ratsJOURNAL OF PINEAL RESEARCH, Issue 4 2004Leila Bikjdaouene Abstract:, We have previously proven that some synthetic kynurenines behave as antagonists of the N-methyl- d -aspartate receptor inhibiting neuronal subtype of nitric oxide synthase activity. We now investigate the anticonvulsant activity of four of these kynurenines in pentylenetetrazole (PTZ)-treated rats. The rats were treated with each kynurenine (10,160 mg/kg, s.c.) 30 min before PTZ administration (100 mg/kg, s.c.). Then, latency, duration and intensity of the first seizure and the percent animal survival were noted. PTZ-induced death was counteracted by high doses of kynurenines. Latency of the first seizure was significantly increased and its intensity reduced at the same doses, whereas the duration of the first seizure significantly decreased with doses of 20 mg/kg in most of the kynurenines tested. Three hours after PTZ administration, the surviving animals were sacrificed and the levels of brain amino acids and nitrite were measured. PTZ administration increased glutamate, glutamine, serine and taurine levels in different brain areas. High doses of kynurenines generally counteracted the effects of PTZ on excitatory amino acids, but they also reduced inhibitory aminoacids. However, the most consistent effect of kynurenines was the dose-dependent reduction of brain nitrite levels induced by PTZ. These results reveal a new family of anticonvulsant drugs that affect mainly to nitric oxide production in the brain. [source] Veterinarians' preferences for anticonvulsant drugs for treating seizure disorders in dogs and catsAUSTRALIAN VETERINARY JOURNAL, Issue 11 2009EK Kluger Objective To identify veterinarians' approaches and concerns when managing canine and feline patients with acute and chronic seizure disorders. Design Cross-sectional survey. Method A questionnaire was distributed to veterinarians to determine how many dogs and cats they were actively treating for seizures, their anticonvulsant drug (ACD) preferences for treating acute and chronic seizure disorders and whether serum anticonvulsant concentrations and/or biochemical analytes were routinely measured. Additional questions involved the respondent's year and place of graduation and identified concerns they faced when managing patients with seizure disorders. Results Phenobarbitone was the most commonly used ACD for managing chronic seizure disorders in both dogs and cats, with 82% of respondents using a combination of phenobarbitone and potassium bromide to manage refractory seizure disorders in dogs. Most respondents (96%) felt comfortable managing seizures in dogs, but only 63% were comfortable managing affected cats. Routine monitoring of serum ACD concentrations and of liver biochemical analytes was performed routinely by 71% and 45% of respondents, respectively. Of the respondents, 86% graduated from Australian universities and of these 53% had graduated after 1985. Conclusion Veterinarians identified when to commence medication, whether regular monitoring of serum ACD concentrations and liver enzyme activity was necessary, and if the cost was justified. Veterinarians also identified the need to balance dose rates and side-effects by using combination therapy, and the importance of providing accurate information to clients about what to expect in terms of seizure control for their pet. [source] The Effect of Oxcarbazepine on Bone MetabolismACTA NEUROLOGICA SCANDINAVICA, Issue 3 2009Y. Çetinkaya Objective,,, Long term use of several antiepileptic drugs is known to cause alteration in bone metabolism. Therefore, we investigated the effect of new antiepileptic drug, oxcarbazepine, on bone metabolism. Methods,,, Twenty eight patients who were on oxcarbazepin therapy (18 female, 10 males; mean age: 27.82 ± 10.98 years (range: 15,45)) with no additional antiepileptic drug use history in one year period prior to the study and 28 control subjects were involved in the study. Measurement of calcium, phosphate, alkaline phosphatase and Vitamin D3 levels and bone density measurements with DEXA method were performed in patient and age-matched control groups. The baseline parameters were compared with the control group and with those measured at the end of one year. Results,,, The biochemical (calcium, phosphate, alkaline phosphatase and Vitamin D3) parameters and densitometry values after one year of therapy were not different than the baseline values indicating that those were not affected by the therapy (P > 0.05). Conclusions,,, In previous studies, anticonvulsant drugs that induce enzymes increase bone degradation by causing vitamin D deficiency. According to the results of this study, oxcarbazepin with little effect on enzyme induction was shown not to affect bone mineral metabolism. [source] Impurities , the hidden danger in anticonvulsant drugsACTA NEUROLOGICA SCANDINAVICA, Issue 2 2008T. P. Sabroe No abstract is available for this article. 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