Adenosine and epilepsy: from therapeutic rationale to new therapeutic strategies.
Adenosine, as the brain's endogenous anticonvulsant, is considered to be responsible for seizure arrest and postictal refractoriness. On the other hand, deficiencies within the adenosine-based neuromodulatory system may contribute to epileptogenesis. Based on these natural mechanisms and on findings that adenosine and its analogs can suppress pharmacoresistant seizures, a new field of adenosine-based therapies has emerged, including the use of adenosine receptor agonists and adenosine transport inhibitors, or the inhibition of adenosine kinase, which is thought to be the key enzyme for the regulation of intra- and extracellular adenosine levels. However, most of these pharmacological approaches are limited by strong systemic side effects ranging from a decrease of heart rate, blood pressure, and body temperature to sedation. Recently, new strategies have been developed aimed at the local reconstitution of the inhibitory adenosinergic tone by intracerebral implantation of cells engineered to release adenosine. Adenosine-releasing cells or devices implanted into or near a seizure focus offer new hopes for a side effect-free therapy for pharmacoresistant epilepsy.
Boison
Detlev
D
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland. boison@pharma.unizh.ch
D000241:Adenosine / Q000172:deficiency* / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D017690:Cell Transplantation / Q000379:methods / Q000639:trends; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology; D033703:Nucleoside Transport Proteins; D058906:Purinergic P1 Receptor Agonists
D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D033703:Nucleoside Transport Proteins; D058906:Purinergic P1 Receptor Agonists; C444719:adenosine transporter; D000241:Adenosine