Could treatment with arundic acid (ONO-2506) increase vulnerability for depression?
Arundic acid (ONO-2506) is believed to be neuroprotective because of its actions on glia cells; i.e., its inhibitory effects on the synthesis of a calcium-binding protein S100B. ONO-2506 is undergoing clinical trials for the treatment of patients with stroke and Alzheimer's disease. Recent clinical studies point to a pervasive comorbidity of depression with stroke and Alzheimer's disease. Previously, S100B has been implicated in the pathobiological mechanisms of depression. Preclinical studies have shown that antidepressant treatment significantly increases brain S100B. Here we hypothesize that available data that link S100B with depression, along with the proposed inhibitory action of ONO-2506 on S100B synthesis, indicate that this compound could increase vulnerability for depression in patients at risk for this disorder, and we propose that evaluation of patients with stroke and Alzheimer's disease for the presence of depression should be routine in clinical trials employing ONO-2506. Although it may be open for discussion whether the neuroprotective effects of ONO-2506 are exclusively due to its inhibition of S100B synthesis, the latter action of ONO-2506 warrants studies of the effects of this drug in the pathobiology of depression.
Manev
Radmila
R
Department of Psychiatry and the Psychiatric Institute, University of Illinois at Chicago, 1601 West Taylor Street, M/C912, Chicago, IL 60612, USA.
Manev
Hari
H
D000544:Alzheimer Disease / Q000188:drug therapy / Q000453:epidemiology; D000818:Animals; D002210:Caprylates / Q000009:adverse effects* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015897:Comorbidity; D003863:Depression / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D009414:Nerve Growth Factors / Q000235:genetics; D018696:Neuroprotective Agents / Q000627:therapeutic use; D012307:Risk Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics; D020521:Stroke / Q000188:drug therapy
D002210:Caprylates; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; C459360:ONO2506; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D005473:Fluoxetine