title: Dimebon inhibits calcium-induced swelling of rat brain mitochondria but does not alter calcium retention or cytochrome C release.
abstract: Dimebon was originally introduced as an antihistamine and subsequently investigated as a possible therapeutic for a variety of disorders, including Alzheimer's disease. One putative mechanism underlying the neuroprotective properties of Dimebon is inhibition of mitochondrial permeability transition, based on the observation that Dimebon inhibited the swelling of rat liver mitochondria induced by calcium and other agents that induce permeability transition. Because liver and brain mitochondria differ substantially in their properties and response to conditions associated with opening of the permeability transition pore, we sought to determine whether Dimebon inhibited permeability transition in brain mitochondria. Dimebon reduced calcium-induced mitochondrial swelling but did not enhance the calcium retention capacity or impair calcium-induced cytochrome C release from non-synaptic mitochondria isolated from rat brain cerebral cortex. These findings indicate that Dimebon does not inhibit mitochondrial permeability transition, induced by excessive calcium uptake, in brain mitochondria.
authors.affiliation: Spinal Cord and Brain Injury Research Center, Department of Anatomy and Neurobiology, University of Kentucky, 741. S. Limestone Street, Lexington, KY 40536-0509, USA.
authors.forename: Kranthi Kumari
authors.initials: KK
authors.lastname: Naga
authors.forename: James W
authors.initials: JW
authors.lastname: Geddes
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007211:Indoles; D045304:Cytochromes c; C010119:latrepirdine; D002118:Calcium