benzofurans and Epilepsy

Epilepsy and CNS injury identify a heterogenous group of diseases, many of which exhibit refractoriness (e.g., the partial epilepsies) to established drug therapy or, as in the case of brain and spinal cord injuries of variable etiologies, remain a formidable target for successful drug development. As such, the search for safe, effective antiepileptic and neuroprotective drugs continues. Although several CNS targets have been identified for drug development, especially the excitatory amino acid receptors, free-radical systems, gangliosides, and nitric oxide, etc., the opioid system and its diversity of receptors have, until recently, received little attention. This review attempts to focus on one opioid system, namely the kappa receptor class of opioid ligands, specifically addressing the potential anticonvulsant and neuroprotective properties of the arylacetamide series of kappa opioid analgesics as novel pharmacotherapeutic approaches to the treatment of epilepsy, stroke, or trauma related brain or spinal cord injury.

Topics: Analgesics, Opioid; Animals; Anticonvulsants; Benzofurans; Central Nervous System Diseases; Epilepsy; Humans; Pyrroles; Pyrrolidines; Receptors, Opioid, kappa; Thiophenes

The aim of this study is to observe the effect of butylphthalide (NBP) on the amino acid content in the brain of epileptic mice.. NBP was injected intraperitoneally into the mice, and acute epileptic mice models were made after 30 minutes. The change of the four amino (aspartic acid, gamma-aminobutyric acid, glutamate, glycine) content in the brain of the epileptic mice was investigated.. The contents of Glu and Glu/GABA (control group: 38.78, NBP high-dose group: 5.52) in the NBP high-dose group were lower compared with the control group. The difference was statistically significant.. NBP could regulate the balance of excitement and inhibition systems by reducing the contents of Glu and Glu/GABA, which might relieve seizures.

Topics: Amino Acids; Animals; Benzofurans; Brain; Epilepsy; gamma-Aminobutyric Acid; Glutamic Acid; Mice

Topics: Animals; Anticonvulsants; Benzofurans; Brain-Derived Neurotrophic Factor; Epilepsy; Pentylenetetrazole; Proto-Oncogene Proteins c-akt; Rats

There is a high need for the development of new and improved antiseizure drugs (ASDs) to treat epilepsy. Despite the potential of marine natural products (MNPs), the EU marine biodiscovery consortium PharmaSea has made the only effort to date to perform ASD discovery based on large-scale screening of MNPs. To this end, the embryonic zebrafish photomotor response assay and the larval zebrafish pentylenetetrazole (PTZ) model were used to screen MNP extracts for neuroactivity and antiseizure activity, respectively. Here we report the identification of the two known isoquinoline alkaloids TMC-120A and TMC-120B as novel antiseizure compounds, which were isolated by bioactivity-guided purification from the marine-derived fungus

Topics: Alkaloids; Animals; Anticonvulsants; Aspergillus; Benzofurans; Disease Models, Animal; Drug Resistance; Epilepsy; Isoquinolines; Larva; Male; Mice; North Sea; Seizures; Zebrafish

Small-conductance Ca(2+)-activated potassium (SK) channels constitute a family of ion channels that are regulated by the cytosolic Ca(2+) concentration. Increases in the intracellular Ca(2+) concentration ([Ca(2+)](i)) result in opening of the channels, which in turn will lead to changes in the membrane potential. As the name implies, the channels are of small conductance, but even so, they are known to play a crucial role in several physiological processes, such as modulation of neurotransmitter and hormone secretion, as well as memory and learning (e.g.,see Curr Med Chem 14:1437-1457, 2007). Owing to the central role of SK channels, they have attracted much attention as potential drug targets, both with respect to identification of activators and blockers of SK channel activity for indications such as, e.g., epilepsy, pain, and urinary incontinence (see Curr Med Chem 14:1437-1457, 2007; Curr Pharm Des 12:397-406, 2006). Thus, great efforts have been put into the development of robust high-throughput assays for detection and characterization of modulators of SK channel activity. In the present chapter, we describe two fluorescence-based Tl(+)influx assays for detection of positive and negative SK channel modulators.

Topics: Benzofurans; Cell Culture Techniques; Cell Line; Epilepsy; Ethers, Cyclic; Humans; Indoles; Ion Channel Gating; Kidney; Membrane Potentials; Oximes; Pain; Small-Conductance Calcium-Activated Potassium Channels; Thallium; Urinary Incontinence

K(+) channels are key modulators of neuronal excitability, and mutations in certain types of these channels are known to cause epileptic seizures. Activation of K(+) channels is reported to suppress epileptic discharge; however, the types of K(+)-channel openers that are most effective as anti-epileptic agents are not well understood. We established a quantitative fluorescence assay using the Na(+) indicator sodium-binding benzofuran isophthalate (SBFI) for evaluation of various compounds on epileptiform activities induced by 4-aminopyridine (4-AP) in cultured rat hippocampal neurons. Among the K(+)-channel openers, the K(V)7.2/K(V)7.3-channel openers retigabine and flupirtine and K(Ca)2-channel openers NS309, DCEBIO, and 1-EBIO showed potent anti-epileptic effects similar to conventional antiepileptic drugs (AEDs). In contrast, the K(Ca)1.1-channel openers NS1619, isopimaric acid, and chlorzoxazone demonstrated moderate inhibition. The K(ir)6-channel openers minoxidil, cromakalim, and pinacidil did not show anti-epileptic effects. We concluded that K(V)7.2/K(V)7.3, K(Ca)2, and, to some extent, K(Ca)1.1-channel openers, but not K(ir)6-channel openers, suppress 4-AP-induced epileptiform activities in hippocampal neurons. These results suggest that the K(+)-channel openers for this category of K(+) channels might have therapeutic potential as new classes of antiepileptic drugs.

Topics: 4-Aminopyridine; Animals; Anticonvulsants; Benzofurans; Cells, Cultured; Epilepsy; Ethers, Cyclic; Fluorescence; Fluorescent Dyes; Hippocampus; Neurons; Potassium Channels; Rats; Rats, Wistar

Topics: Animals; Avoidance Learning; Benzofurans; Epilepsy; Female; Hippocampus; Lactones; Memory; Rats; Rats, Inbred Strains

Topics: Animals; Anticonvulsants; Benzofurans; Brain; Epilepsy; Female; Lactones; Rats; Rats, Inbred Strains