title: Possible sites of therapeutic action in restless legs syndrome: focus on dopamine and α2δ ligands.
abstract: Restless legs syndrome (RLS) is a common sensorimotor disorder characterized by abnormal sensations that occur primarily at rest or during sleep, which are alleviated by movement of the affected limb. The pathophysiology of RLS remains unclear, although roles for dopamine dysfunction and brain iron deficiency have been proposed. The hypothalamic A11 dopaminergic circuit is used to explain the dopamine dysfunction in RLS and the potential therapeutic actions of dopamine D(2) agonists. Modulation of central and peripheral neuronal circuits may also explain the potential therapeutic sites of action of opioids, adenosine receptor ligands, and voltage-gated calcium channel α(2)δ ligands in RLS. The known and possible therapeutic benefits of these agents and their relationship to dopaminergic dysfunction in RLS are discussed in this review.
authors.affiliation: Pfizer Inc., 235 East 42nd Street, New York, N.Y. 10017, USA. andrew.thorpe@pfizer.com
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thorpe
authors.forename: Andrew
authors.initials: A
authors.lastname: Clair
authors.forename: Shawn
authors.initials: S
authors.lastname: Hochman
authors.forename: Stefan
authors.initials: S
authors.lastname: Clemens
mesh_terms: D015220:Calcium Channels / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism* / Q000627:therapeutic use; D049670:History, 17th Century; D049671:History, 18th Century; D049672:History, 19th Century; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008024:Ligands; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D018047:Receptors, Purinergic P1; D012148:Restless Legs Syndrome / Q000188:drug therapy* / Q000266:history / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology
chemical_list: C425903:CACNA2D1 protein, human; D015220:Calcium Channels; D008024:Ligands; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid; D018047:Receptors, Purinergic P1; D004298:Dopamine