title: L-type calcium channels as drug targets in CNS disorders.
abstract: L-type calcium channels are present in most electrically excitable cells and are needed for proper brain, muscle, endocrine and sensory function. There is accumulating evidence for their involvement in brain diseases such as Parkinson disease, febrile seizures and neuropsychiatric disorders. Pharmacological inhibition of brain L-type channel isoforms, Cav1.2 and Cav1.3, may therefore be of therapeutic value. Organic calcium channels blockers are clinically used since decades for the treatment of hypertension, cardiac ischemia, and arrhythmias with a well-known and excellent safety profile. This pharmacological benefit is mainly mediated by the inhibition of Cav1.2 channels in the cardiovascular system. Despite their different biophysical properties and physiological functions, both brain channel isoforms are similarly inhibited by existing calcium channel blockers. In this review we will discuss evidence for altered L-type channel activity in human brain pathologies, new therapeutic implications of existing blockers and the rationale and current efforts to develop Cav1.3-selective compounds.
authors.affiliation: a Department of Pharmacology and Toxicology ; Center for Molecular Biosciences ; University of Innsbruck ; Innsbruck , Austria.
authors.forename: Nadine J
authors.initials: NJ
authors.lastname: Ortner
authors.affiliation: a Department of Pharmacology and Toxicology ; Center for Molecular Biosciences ; University of Innsbruck ; Innsbruck , Austria.
authors.forename: Jörg
authors.initials: J
authors.lastname: Striessnig
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002493:Central Nervous System Diseases / Q000188:drug therapy; D006801:Humans
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type
keywords: Cav1.2; Cav1.3; L-type calcium channels; drug selectivity; neuropsychiatric disorders; pharmacology; voltage-gated calcium channels