Progress in neuro-psychopharmacology & biological psychiatry
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2015
ReviewTargeting drug sensitivity predictors: New potential strategies to improve pharmacotherapy of human brain disorders.
One of the main challenges in medicine is the lack of efficient drug therapies for common human disorders. For example, although depressed patients receive powerful antidepressants, many often remain resistant to psychopharmacotherapy. ⋯ Here, we apply the concept of endophenotypes and their interplay to drug action and sensitivity. Based on these analyses, we postulate that novel drugs may be developed by targeting specific molecular pathways that integrate drug targets with drug sensitivity predictors.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2015
m-Trifluoromethyl-diphenyl diselenide, a multi-target selenium compound, prevented mechanical allodynia and depressive-like behavior in a mouse comorbid pain and depression model.
Chronic pain and depression are two complex states that often coexist in the clinical setting and traditional antidepressants and analgesics have shown limited clinical efficacy. There is an intricate communication between the immune system and the central nervous system and inflammation has been considered a common mediator of pain-depression comorbidity. This study evaluated the effect of m-trifluoromethyl diphenyl diselenide [(m-CF3-PhSe)2], an organoselenium compound that has been reported to have both antinociceptive and antidepressant-like actions, in the comorbidity of chronic pain and depression induced by partial sciatic nerve ligation (PSNL) in an inflammatory approach. ⋯ These effects could be mainly associated with an anti-inflammatory action of (m-CF3-PhSe)2 which reduced the levels of pro-inflammatory cytokines, NF-κB and COX-2, and p38 MAPK activation that were increased by PSNL. (m-CF3-PhSe)2 also increased the BDNF levels and reduced glutamate release and 5-HT uptake altered by PSNL. Although acute and subchronic treatments with (m-CF3-PhSe)2 prevented these alterations induced by PSNL, the best results were found when (m-CF3-PhSe)2 was subchronically administered to mice. Considering the potential common mechanisms involved in the comorbidity of inflammation-induced depression and chronic pain, the results found in this study indicate that (m-CF3-PhSe)2 could become an interesting molecule to treat long-lasting pathological pain associated with depression.