Anticonvulsants
H. Y. Wong Steven in Therapeutic Drug Monitoring and Toxicology by Liquid Chromatography, 2017
The successful treatment of seizures with anticonvulsant drugs began in 1857 with the discovery by Charles Locock that potassium bromide reduced the frequency of seizures in some of his patients with epilepsy. Fifty-five years then passed before Hauptman presented an account of his experience with phénobarbital as an anticovulsant drug. The pharmacological response to a drug is a result of the interaction of the drug with tissue receptors controlling that response. Despite the large number of drugs available, however, six drugs are the principal agents being used in treating patients with epilepsy: phenytoin, phénobarbital, primidone, carbamazepine, ethosuximide, and valproic acid. The clinical pharmacology of six drugs is summarized and their clinical manifestations of toxicity are presented. The measurement of anticonvulsant drug concentrations is always useful in the detection of patient noncompliance with a prescribed regimen. The chapter describes HPLC analysis of vaîproic acid and these procedures require either postcolumn reactions or precolumn derivatization.
Benzodiazepines: Anticonvulsant and other clinical uses
Adam Doble, Ian L Martin, David Nutt in Calming the Brain: Benzodiazepines and related drugs from laboratory to clinic, 2020
Benzodiazepines are among the most potent and best-tolerated anticonvulsant agents known. However, their use as antiepileptic agents has been limited by the rapid development of tolerance to their prophylactic effect and to rebound seizures upon treatment interruption. The deleterious effects of benzodiazepines on vigilance and cognitive function are also evidently a drawback in the use of benzodiazepines as antiepileptic agents over long time periods. The principal therapeutic uses of flumazenil are to reverse the effects of benzodiazepines when used in anaesthesia and in the treatment of coma resulting from benzodiazepine overdose. Many of the psychotropic effects of benzodiazepines make them appropriate for use as anaesthetic agents, or as adjuncts to anaesthesia. The introduction of flumazenil has been of considerable importance in the use of midazolam and other benzodiazepines in anaesthesia. A further use of benzodiazepines is in the treatment of alcohol withdrawal.
Anticonvulsant Drugs during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
Pharmacokinetics of several anticonvulsants showed that the levels of phenytoin and phenobarbital decreased during pregnancy associated with physiologic changes of pregnancy affect metabolism, plasma protein binding, maternal serum level, and clearance of anticonvulsants. Anticonvulsant levels should be monitored throughout pregnancy in order to control seizure activity which may increase in some pregnant women. Certain anticonvulsants, especially the hydantoins, may be associated with folic acid anemia and may depress vitamin D. Therefore, vitamin and folic acid supplements have been recommended for the pregnant woman with epilepsy who is taking anticonvulsant medications. Phenytoin is a hydantoin, and has been used as an anticonvulsant for over 100 years. It is chemically related to barbiturates, is also used to treat arrhythmias, trigeminal neuralgia, and myotonic muscular dystrophy. Carbamazepine is a widely prescribed anticonvulsant, also used as analgesic for the trigeminal neuralgia and in psychiatry as a mood stabilizer.
New similarity-based algorithm and its application to classification of anticonvulsant compounds
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2007
Alan Talevi, Julián J. Prieto, Luis E. Bruno-Blanch, Eduardo A. Castro
A similarity-based algorithm based on a previously developed model is applied in the classification of two sets of anticonvulsant and non-anticonvulsant drugs. Each set is composed of a) anticonvulsant compounds that have shown moderate to high activity in the Maximal Electroshock Seizure (MES) test and b) drugs with other biological activities or poor activity in the MES test. The results from the analysis of variance (ANOVA) indicate that the proposed algorithm is able to differentiate anticonvulsant from non-anticonvulsant drugs. The proposed model may then be useful in the identification of new anticonvulsant agents through virtual screening of large virtual libraries of chemical structures.
Synthesis and anticonvulsant activity evaluation of 6-substituted-[1,2,4]triazolo[3,4-a](tetrazolo[5,1-a])phthalazine derivatives
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2013
Ming Bian, Xian-Qing Deng, Guo-Hua Gong, Cheng-Xi Wei, Zhe-Shan Quan
With the aim of finding new anticonvulsant drugs, new 6-substituted-[1,2,4]triazolo[3,4-a] (tetrazolo[5,1-a]) phthalazine derivatives (1–34) have been designed and synthesized. All the compounds were evaluated for their anticonvulsant activities using the maximal electroshock test (MES). Most of the synthesized compounds exhibited potent anticonvulsant activities in the MES. The most promising compound 14 showed significant anticonvulsant activity in MES test with ED50 value of 9.3 mg/kg. It displayed a wide margin of safety with protective index much higher than the standard drug Carbamazepine. And the potency of compound 14 against seizures induced by Pentylenetetrazole, Isoniazid, Thiosemicarbazide and 3-Mercaptopropionic acid in the chemical-induced seizure tests suggested that compound 14 displayed wide spectrum of activity in several models.
Chrysin isolated from
Published in Nutritional Neuroscience, 2019
Priyanka Sharma, Amita Kumari, Ashu Gulati, Sairam Krishnamurthy, Siva Hemalatha
Objective: The traditional use of the ethanolic extract of the fruit of Pyrus pashia (EPP) as a potential anticonvulsant was validated using experimental animal models. Furthermore, the anticonvulsant activity of isolated chrysin was investigated against experimental animal models to draw a possible therapeutic mechanism of EPP. Additionally, the safety profile of chrysin was evaluated to explore the possible therapeutic alternative in the management of epilepsy. Method: The anticonvulsant activity in terms of duration of onset of hind limb tonic extension and convulsion of standardized EPP was evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ) model of experimental epilepsy respectively. Furthermore, the anticonvulsant activity and electrophysiological properties of chrysin was investigated in addition to antioxidant activity against PTZ-induced convulsion in experimental animals. Moreover, the neurotoxic profile of the chrysin was assessed in terms of duration of movement and running in photoactometer and rotarod apparatus, respectively. Results: EPP (100, 200, and 400 mg/kg) exhibited significant anticonvulsant activity against an acute model of MES and PTZ-induced convulsions in experimental animals. Furthermore, chrysin (2.5, 5, and 10 mg/kg) also exhibited significant anticonvulsant activity against PTZ-induced convulsions in rats. In addition, chrysin did not exhibit sedative-like behavior in experimental rodents. Discussion: EPP could be considered as a potential and alternative therapeutic option in the management of epilepsy.
Related Knowledge Centers
- Excitotoxicity
- Neuropathic Pain
- Epilepsy
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- Pharmacology
- Epileptic Seizure
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