Peptide compounds used for treating diseases associated with hyperexcitability disorders and dysfunction of an ion channel
An overexcited, compound technology, applied in the screening of compounds, active ingredients of heterocyclic compounds, resistance to vector-borne diseases, etc.
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0294] Initial studies showed that lacosamide alters the rapid inactivation of sodium channel gating in a manner inconsistent with the effects of existing antiepileptic agents. This is evidenced by the very limited effect of lacosamide on action potential initiation induced by brief depolarization steps or ramps. The lack of effect of lacosamide on rapid inactivation is further supported by experiments performed on Xenopus oocytes expressing only the alpha subunit of the sodium channel. Furthermore, lacosamide did not alter the rapid inactivation voltage profile or delay its recovery from steady-state rapid inactivation, as observed in neuroblastoma cells. In contrast to lacosamide having no effect, carbamazepine, lamotrigine and phenytoin all significantly altered these gating processes.
[0295] However, lacosamide still rapidly and profoundly inhibited sodium currents in a voltage-dependent manner in the oocyte expression system. Sodium channels in mouse neuroblastoma N1E...
Embodiment 2
[0314] Example 2: Lacosamide in a Stress-Induced Anxiety Animal Model
[0315] In the study the effects of lacosamide were tested in an animal model of stress-related anxiety. In this animal model, stress is induced by measuring rectal temperature. The stress-induced hyperthermia (SIH) test is based on the principle that mice have an innate hyperthermic response to stress that reflects levels of stress-induced anxiety. In this model, the effect of lacosamide was compared with that of the reference compound chlordiazepoxide (CDP), which is used clinically as a first-line anxiolytic treatment. In addition, the new anticonvulsant pregabalin, which was also developed for generalized anxiety disorders, was used as an additional reference compound.
[0316] Materials and methods
[0317] Adult male 129SVEV mice (8 weeks old) from Taconic Laboratories (Germantown, NY) were used in this study. Mice were housed in standard polycarbonate cages with filter tops. Four animals were ho...
Embodiment 3
[0326] The focus of this study was to analyze the potential neuroprotective effects of lacosamide in rat hippocampus slice cultures after exposure to glutamate (Glut) as a model of excitotoxic injury. Lacosamide was administered 2 hours before injury and until the end of the experiment 24 hours after injury. Quantification of necrotic cell death was performed by propidium iodide (PI) uptake (neuronal cell death in the CA1-CA3 region) and lactate dehydrogenase (LDH) release (cell death throughout the slice). Lacosamide shows protective effect against necrotic cell death after Glut. Due to the neuroprotective effects found in this study, lacosamide is speculated to be effective in the treatment of disorders associated with excitotoxic injury.
[0327] experimental method
[0328] Model system: organotypic hippocampal slice culture (OHC).
[0329] Organotypic slice cultures, where hippocampal slice cultures represent in vitro models that preserve distinct cell types and mainta...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More