Kappa opioids: therapeutic considerations in epilepsy and CNS injury.
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.
Tortella
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Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100, USA.
DeCoster
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D000701:Analgesics, Opioid / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001572:Benzofurans / Q000494:pharmacology; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D011758:Pyrroles / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D013876:Thiophenes / Q000494:pharmacology
D000701:Analgesics, Opioid; D000927:Anticonvulsants; D001572:Benzofurans; D011758:Pyrroles; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D013876:Thiophenes; C054718:PD 117302; C067110:enadoline