Subtype-selective GABAA receptor mimetics--novel antihyperalgesic agents?
Agonists at the benzodiazepine-binding site of ionotropic gamma-aminobutyric acid (GABA(A)) receptors are in clinical use as hypnotics, anxiolytics, and anticonvulsants since the early 1960. Analgesic effects of classical benzodiazepines have occasionally been reported in certain subgroups of patients suffering from chronic pain or after spinal delivery through intrathecal catheters. However, these drugs are generally not considered as analgesics but should in fact be avoided in patients with chronic pain. Recent evidence from genetically modified mice now indicates that agents targeting only a subset of benzodiazepine (GABA(A)) receptors should provide pronounced antihyperalgesic activity against inflammatory and neuropathic pain. Several such compounds have been developed recently, which exhibit significant antihyperalgesia in mice and rats and appear to be devoid of the typical side-effects of classical benzodiazepines.
Zeilhofer
Hanns Ulrich
HU
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland. zeilhofer@pharma.uzh.ch
Witschi
Robert
R
Hösl
Katharina
K
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018755:GABA Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D058785:GABA-A Receptor Agonists; D006801:Humans; D008140:Lorazepam; D009437:Neuralgia / Q000503:physiopathology / Q000517:prevention & control; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D021122:Protein Subunits / Q000819:agonists / Q000378:metabolism / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology
D000700:Analgesics; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D021122:Protein Subunits; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D008140:Lorazepam