ucb L059, a novel anti-convulsant drug: pharmacological profile in animais (original) (raw)
Related papers
AJB carvacrol borneol citral anticonvulsant2010
Carvacrol, a monoterpenic phenol present in essential oils of the Labiatae family, has been used through the ages as a source of flavor in food and for medicinal purposes. Borneol is a monoterpene found in several species of Artemisia and Dipterocarpaceae, used for anxiety, pain and anesthesia in traditional Chinese. Citral, a mixture of two geometrical isomers (neral and geranial), is one of the most important compounds in some citrus oils and has central nervous system (CNS) properties. The anticonvulsant effect of carvacrol (CARV), (− − − −)-borneol (BOR) and citral (CIT) was investigated in two animal models of epilepsy. Mice were pretreated with CARV, BOR or CIT (50, 100, and 200 mg/kg, i.p.) 30 min before pentylenetetrazole (PTZ) or maximal electroshock (MES) tests, the two most important animal epilepsy tests. The latency for development of convulsions and protection percentage was recorded. In order to investigate the involvement of GABAergic system, flumazenil was utilized. These monoterpenes, CARV in a higher, but not in a lower dose (p < 0.001), BOR and CIT in all doses (p < 0.05 or p < 0.001), were capable of promoting an increase of latency for the development of convulsions induced by PTZ. Additionally, these compounds were efficient in preventing the tonic convulsions (p < 0.05) induced by MES. However, the GABAergic neurotransmitter system might be involved, at least in BOR effects. Henceforth, our results suggest that CARV, BOR and CIT possess anticonvulsant activity effect against PTZ-induced convulsions and MES.
RECENT DEVELOPMENTS ON ANTI-CONVULSANTS
Epilepsy is not a disease, but a syndrome of different cerebral disorders of the CNS. This syndrome is characterized by paroxysmal, excessive, and hypersynchronous discharges of large numbers of neurons. The first major division of epilepsy is localization-related (i.e., focal, local, partial) epilepsies, which account for about 60% of all epilepsies. The remainder, about 40%, is composed of generalized epilepsies. The most common, and most difficult to treat, seizures in Adult patients are complex partial seizures, whereas primary generalized tonic-clonic (formerly, “Grand mal" epilepsy) seizures respond in most patients to treatment with anticonvulsants. Thus a need for new drugs with a greater benefit as related to side effects and tolerability, even at the expense of efficacy, when compared to the existing antiepileptic agents.
The Pharmacology and Toxicology of Third-Generation Anticonvulsant Drugs
Journal of Medical Toxicology, 2017
Epilepsy is a neurologic disorder affecting approximately 50 million people worldwide, or about 0.7% of the population [1]. Thus, the use of anticonvulsant drugs in the treatment of epilepsy is common and widespread. There are three generations of anticonvulsant drugs, categorized by the year in which they were developed and released. The aim of this review is to discuss the pharmacokinetics, drug-drug interactions, and adverse events of the third generation of anticonvulsant drugs. Where available, overdose data will be included. The pharmacokinetic properties of third-generation anticonvulsant drugs include relatively fewer drug-drug interactions, as well as several unique and life-threatening adverse events. Overdose data are limited, so thorough review of adverse events and knowledge of drug mechanism will guide expectant management of future overdose cases. Reporting of these cases as they occur will be necessary to further clarify toxicity of these drugs.
A Review: Animal Models for Screening Antiepileptic Drugs & Important Unani Anticonvulsant Drugs
Epilepsy is the world's most common serious disorder of the brain according to WHO. It is defined as the occurrence of transient paroxysms of excessive or uncontrolled discharges of neurons due to a number of causes leading to epileptic seizures. The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. A large number of traditional drugs have been used in epilepsy since centuries. So, screening/investigating these drugs for their anticonvulsant activity to make an effective medicine in the treatment of epilepsy is auspicious. Different types of experimental models have been used to assess the anticonvulsant activity of these drugs such as Maximal electroshock seizure (MES) test, Pentylenetetrazole (PTZ) test, kindling animal model, strychnine model etc. These models can be either in vivo or in vitro, mechanism specific, mechanism independent, or seizure specific. The present article explains the types of experimental models used for screening of anticonvulsant activity of traditional drugs and some important scientifically proved Unani anticonvulsant drugs.
Drug Development Research, 1989
U-54494A and its enantiomers were administered to mice orally, intravenously, and intracerebroventricularly, and the anticonvulsant time courses were assessed by determination of electroshock seizure thresholds. The time courses of brain concentrations of the administered compounds were also assessed by an HPLC-electrochemical detection assay. The racemate (U-54494A) and both enantiomers were found to be long-acting anticonvulsants with high oral apparent bioavailabilities. However, this was not reflected by the brain concentrations of administered compound; during the protracted anticonvulsant time courses, the drugs were present at only very low levels in the brain. This suggests the possibility of active metabolites contributing to the anticonvulsant effects of U-54494A. However, both the enantiomers and the racemate are intrinsically active as indicated by anticonvulsant effects elicited via intracerebroventricular administration. Thus, both of the enantiomers and metabolites thereof contribute to the anticonvulsant effects of U-54494A.
Current Topics in Medicinal Chemistry, 2012
Major advances in antiepileptic drug therapy have taken place since 1950s. In the first period, several antiepileptic drugs (AEDs) such as phenobarbital, diphenylhydantoin, ethosuximide, carbamazepine, benzodiazepines and valproic acid were introduced to epilepsy treatment. After 1990 many new generation drugs (lamotrigine, topiramate, gabapentine, pregabaline, felbamate, lacosamide, levetiracetam etc.) have been developed. These novel AEDs have offered some advantages such as fewer side effects, fewer drug-drug interactions, and better pharmacokinetic properties. But pharmacoresistance and therapeutic failure in 20-25% of the patients remain the main reasons to continue efforts to find safer and more efficacious drugs and ultimate a treatment for this devastating disease. Several AEDs especially novel compounds have been found to be effective also in the treatment of several other neurologic and psychiatric disorders. Chemical diversity of the newer antiepileptic drugs as well as those currently in clinical development is another point that encourages medicinal chemists to study this subject. This review summarizes recent studies on the development of potential anticonvulsant compounds in different chemical structures, their structure-activity relationships and also therapeutic usages of AEDs other than epilepsy.
Carvacrol,(−)-borneol and citral reduce convulsant activity in rodents
African Journal of …, 2010
Carvacrol, a monoterpenic phenol present in essential oils of the Labiatae family, has been used through the ages as a source of flavor in food and for medicinal purposes. Borneol is a monoterpene found in several species of Artemisia and Dipterocarpaceae, used for anxiety, pain and anesthesia in traditional Chinese. Citral, a mixture of two geometrical isomers (neral and geranial), is one of the most important compounds in some citrus oils and has central nervous system (CNS) properties. The anticonvulsant effect of carvacrol (CARV), (− − − −)-borneol (BOR) and citral (CIT) was investigated in two animal models of epilepsy. Mice were pretreated with CARV, BOR or CIT (50, 100, and 200 mg/kg, i.p.) 30 min before pentylenetetrazole (PTZ) or maximal electroshock (MES) tests, the two most important animal epilepsy tests. The latency for development of convulsions and protection percentage was recorded. In order to investigate the involvement of GABAergic system, flumazenil was utilized. These monoterpenes, CARV in a higher, but not in a lower dose (p < 0.001), BOR and CIT in all doses (p < 0.05 or p < 0.001), were capable of promoting an increase of latency for the development of convulsions induced by PTZ. Additionally, these compounds were efficient in preventing the tonic convulsions (p < 0.05) induced by MES. However, the GABAergic neurotransmitter system might be involved, at least in BOR effects. Henceforth, our results suggest that CARV, BOR and CIT possess anticonvulsant activity effect against PTZ-induced convulsions and MES.
Evaluation of the Effect of Jobelyn® on Chemoconvulsants- Induced Seizure in Mice
Introduction: Epilepsy is a common central nervous system (CNS) disorder characterized by seizures resulting from episodic neuronal discharges. The incidence of toxicity and refractoriness has compromised the clinical efficacy of the drugs currently used for the treatment of convulsions. Thus, there is a need to search for new medicines from plant origin that are readily available and safer for the control of seizures. Jobelyn ® (JB) is a unique African polyherbal preparation used by the natives to treat seizures in children. This investigation was carried out to evaluate whether JB has anti-seizure property in mice.