New antidepressant drugs that do not cross the blood-brain barrier.
Stimulation of neurogenesis in the adult brain (i.e. in the hippocampus) has recently been proposed as a putative mechanism of antidepressant action of drugs. This effect of antidepressants may not be achieved by their primary action on proliferating cells, but may involve the drug-triggered mobilization of trophic factors, such as brain-derived neurotrophic factor (BDNF), glia-derived protein S100 beta, or insulin-like growth factor I (IFG-I). Whereas BDNF and S100 beta are produced in the brain, IGF-I is primarily released from peripheral tissues. Administered peripherally, IGF-I increases hippocampal neurogenesis in the adult rat. Because synthesis and release of IGF-I appear to be stimulated by serotonergic mechanisms, we propose that antidepressants that affect serotonergic mechanisms might be rendered more effective by mobilizing IGF-I. Moreover, we suggest that new antidepressant drugs could be designed that would not enter into the brain but would stimulate peripheral mediators such as IGF-I.
Manev
H
H
Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago, 606912, USA. hmanev@psych.uic.edu
Manev
R
R
D000818:Animals; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051381:Rats
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D007334:Insulin-Like Growth Factor I