Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing body of evidence indicate that besides the central nervous system, antiepileptic drugs may also affect the immunoactivity. Experimental data showed that classical antiepileptic drugs affect peripheral immunological parameters. To this end, phenytoin and carbamazepine attenuate both humoral and cellular response, and an engagement of CD8+ cells in these effects was suggested. Other authors reported that valproate and phenobarbital diminished humoral response and lymphocyte T cytotoxicity in mice, respectively. On the other hand, withdrawal of carbamazepine and phenytoin enhanced autoimmune response in experimental encephalomyelitis in mice. Few data concern effects of new antiepileptic drugs on immune system. It was found that topiramate reversed seizures-induced decrease in lymphocyte T proliferative activity in rats. Some new antiepileptic drugs, e.g., felbamate, stiripentol, loreclezole and tiagabine suppress mitogenes-stimulated proliferative activity of mouse splenocytes in vitro. Results of clinical studies indicate that phenytoin, carbamazepine, and valproate, show immunosuppressive activity, inhibit protein synthesis in lymphocytes, decrease CD4+/CD8+ ratio, decrease IgA, and induce changes in IgG and IgM plasma levels. Cytokine synthesis is also affected by antiepileptic drugs, although in a complex manner. Carbamazepine inhibits IL-2 and IL-4 but stimulates IL-10 and TGFb production in vitro. Treatment of epileptic patients with carbamazepine increases IL-2 level, whereas phenytoin elevates IL-1 blood concentration. In vitro valproate inhibits TNFa and IL-6 production, whereas in epileptic patients this drug enhances IL-1, IL-6 and IL-5 concentration. With respect to undesired effects of antiepileptic drugs, lamotrigine, carbamazepine, phenobarbital and phenytoin may induce hypersensitivity of immune system. The suggested mechanism of the hypersensitivity involves activation of drug specific CD4+ and CD8+, increase in IL-4 and IL-5 level, receptor T polymorphism or direct interaction of drug with lymphocyte T receptors. Summing up, majority of antiepileptic drugs show immunosuppressive effects, however under certain conditions they can also stimulate immune system. Further studies on chronic administration of traditional and new antiepileptic drugs on immune system activity are warranted.
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PMID:[Effects of antiepileptic drugs on immune system]. 1920 64

Progressive multiple sclerosis is associated with metabolic failure of the axon and excitotoxicity that leads to chronic neurodegeneration. Global sodium-channel blockade causes side effects that can limit its use for neuroprotection in multiple sclerosis. Through selective targeting of drugs to lesions we aimed to improve the potential therapeutic window for treatment. This was assessed in the relapsing-progressive experimental autoimmune encephalomyelitis ABH mouse model of multiple sclerosis using conventional sodium channel blockers and a novel central nervous system-excluded sodium channel blocker (CFM6104) that was synthesized with properties that selectively target the inflammatory penumbra in experimental autoimmune encephalomyelitis lesions. Carbamazepine and oxcarbazepine were not immunosuppressive in lymphocyte-driven autoimmunity, but slowed the accumulation of disability in experimental autoimmune encephalomyelitis when administered during periods of the inflammatory penumbra after active lesion formation, and was shown to limit the development of neurodegeneration during optic neuritis in myelin-specific T cell receptor transgenic mice. CFM6104 was shown to be a state-selective, sodium channel blocker and a fluorescent p-glycoprotein substrate that was traceable. This compound was >90% excluded from the central nervous system in normal mice, but entered the central nervous system during the inflammatory phase in experimental autoimmune encephalomyelitis mice. This occurs after the focal and selective downregulation of endothelial p-glycoprotein at the blood-brain barrier that occurs in both experimental autoimmune encephalomyelitis and multiple sclerosis lesions. CFM6104 significantly slowed down the accumulation of disability and nerve loss in experimental autoimmune encephalomyelitis. Therapeutic-targeting of drugs to lesions may reduce the potential side effect profile of neuroprotective agents that can influence neurotransmission. This class of agents inhibit microglial activity and neural sodium loading, which are both thought to contribute to progressive neurodegeneration in multiple sclerosis and possibly other neurodegenerative diseases.
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PMID:Lesional-targeting of neuroprotection to the inflammatory penumbra in experimental multiple sclerosis. 2428 15