The role and therapeutic potential of 5-HT-moduline in psychiatry.
The endogenous neuropeptide, 5-HT-moduline, selectively and allosterically interacts with 5-HT(1B) receptors. By binding at a site distinct from that bound by 5-HT, 5-HT-moduline induces structural changes in 5-HT(1B) receptors or stabilizes a particular conformation of these receptors. These conformational changes ultimately lead to the prevention of 5-HT binding resulting in desensitization of these receptors and reduction of the serotonergic function. The efficacy of 5-HT(1B) receptor agonists, for example, has been shown to be reduced by this peptide in vitro and behaviorally. In addition, 5-HT-moduline increases 5-HT release, which is regulated by presynaptic 5-HT(1B) autoreceptors. The release of 5-HT-moduline itself is increased after acute restraint stress in rats, whereas deactivation of 5-HT-moduline by specific antibodies in mice prevents the development of anxiety in a classic behavioral model, suggesting a potential role of the peptide in the control of anxiety. It is thus hypothesized that agents inhibiting the effect of 5-HT-moduline could have anxiolytic activity. Because the serotonergic activity is known to play a key role in psychiatric disorders such as depression and anxiety, compounds capable of mimicking or inhibiting the activity of 5-HT-moduline can represent novel antidepressants or anxiolytics.
Moret
Chantal
C
NeuroBiz Consulting and Communications, Castres, France. chantal.moret@neurobiz.com
Grimaldi
Brigitt
B
Massot
Olivier
O
Fillion
Gille
G
D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy*; D009479:Neuropeptides / Q000494:pharmacology* / Q000627:therapeutic use*; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use*; D011985:Receptors, Serotonin / Q000187:drug effects
C102005:5-HT-moduline; D000928:Antidepressive Agents; D009479:Neuropeptides; D009842:Oligopeptides; D011985:Receptors, Serotonin; D004298:Dopamine