Latrepirdine dihydrochloride (Dimebolin dihydrochloride) is an orally active, and neuroactive antagonist of multiple drug targets, including histamine receptors, GluR, and 5-HT receptors, used as an antihistamine drug.

Latrepirdine increases succinate dehydrogenase activity (MTT-assay), mitochondrial membrane potential (DeltaPsim), and cellular ATP levels in primary mouse cortical neurons and human neuroblastoma cells (SH-SY5Y). Latrepirdine enhances mitochondrial function both in the absence and presence of stress and Dimebon-treated cells are partially protected to maintain cell viability. [1] Latrepirdine leads to enhanced mTOR- and Atg5-dependent autophagy in cultured mammalian cells. [2] latrepirdine stimulates MTOR- and ATG5-dependent autophagy, leading to the reduction of intracellular levels of APP metabolites, including Aβ in cultured cells. [3] Latrepirdine stimulates the degradation of α-syn in differentiated SH-SY5Y neurons, and in mouse brain following chronic administration, in parallel with elevation of the levels of markers of autophagic activity. [4] Latrepirdine increases intracellular ATP levels and glucose transporter 3 translocation to the plasma membrane in primary neuron. [5]

Latrepirdine treatment of TgCRND8 transgenic mice is associated with improved learning behavior and with a reduction in accumulation of Aβ42 and α-synuclein. [2] Latrepirdine administration results in increased levels of the biomarkers thought to correlate with autophagy activation in the brains of TgCRND8 (APP K670M, N671L, V717F) or wild-type mice, and that treatment is associated with abrogation of behavioral deficit, reduction in Aβ neuropathology, and prevention of autophagic failure among TgCRND8 mice. [3]