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Updated: Jan 28, 2026

Multi-Faceted Mass Spectrometric Investigation of Neuropeptides in Callinectes sapidus
Published on: May 31, 2022
Are neuropeptides relevant for the mechanism of action of SSRIs?
Miłosz Gołyszny1, Ewa Obuchowicz1
1Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland.
Abstract:
Selective serotonin reuptake inhibitors (SSRIs) are drugs of first choice in the therapy of moderate to severe depression and anxiety disorders. Their primary mechanism of action is via influence of the serotonergic (5-HT) system, but a growing amount of data provides evidence for other non-monoaminergic players in SSRI effects. It is assumed that neuropeptides, which play a role as neuromodulators in the CNS, are involved in their mechanism of action. In this review we focus on six neuropeptides: corticotropin-releasing factor - CRF, galanin - GAL, oxytocin - OT, vasopressin - AVP, neuropeptide Y - NPY, and orexins - OXs. First, information about their roles in depression and anxiety disorders are presented. Then, findings describing their interactions with the 5-HT system are summarized. These data provide background for analysis of the results of published preclinical and clinical studies related to SSRI effects on the neuropeptide systems. We also report findings showing how modulation of neuropeptide transmission influences behavioral and neurochemical effects of SSRIs. Finally, future research necessary for enriching our knowledge of SSRI mechanisms of action is proposed. Recognition of new molecular targets for antidepressants will have a significant effect on the development of novel therapeutic strategies for mood-related disorders.
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