The international journal of neuropsychopharmacology
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Int. J. Neuropsychopharmacol. · Dec 2014
The mood stabilizer lithium potentiates the antidepressant-like effects and ameliorates oxidative stress induced by acute ketamine in a mouse model of stress.
Evidence suggests that mammalian target of rapamycin activation mediates ketamine's rapid but transient antidepressant effects and that glycogen synthase kinase-3β inhibits this pathway. However, ketamine has associated psychotomimetic effects and a high risk of abuse. The mood stabilizer lithium is a glycogen synthase kinase-3 inhibitor with strong antisuicidal properties. Here, we used a mouse stress model to investigate whether adjunct lithium treatment would potentiate ketamine's antidepressant-like effects. ⋯ Our results suggest a novel therapeutic strategy and justify the use of lithium in patients who benefit from ketamine.
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Int. J. Neuropsychopharmacol. · Dec 2014
Preclinical to clinical translation of CNS transporter occupancy of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.
Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters. ⋯ These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.