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Merging of pineal neurochemicals. Pharmacological profiles and neurogenic potential

AuthorsFuente Revenga, Mario de la; Fernández-Sáez, Nerea ; Pérez, Concepción; Morales-García, José A. ; Alonso-Gil, Sandra ; Pérez Castillo, Ana ; Yáñez, Matilde; Rodríguez-Franco, María Isabel
Issue Date2013
PublisherSociedad Española de Química Terapéutica
CitationXVII National Meeting of SEQT (2013)
AbstractThe neurohormone melatonin and the natural occurring ß-carboline pinoline are produced in the pineal gland, and both have been found in various human tissues. Melatonin has been widely investigated; especially its effects mediated via MT1 and MT2 GPCRs and antioxidant properties. Its role supporting mitochondrial function and its likely additional actions mediated via nuclear receptors are gaining weight in the recent years, opening a vast field of study beyond MT1 and MT2 receptors. Pinoline is a much potent antioxidant than melatonin found in similar concentrations to melatonin in different tissues, but its pharmacology remains much less studied. Melatonin's chronobiological role as circadiam rhythm regulator is well known while the main role of pinoline in the organism remains unknown. It has been speculated that it may play an important role in sleep pattern and the dreaming process. Besides its antioxidant properties, pinoline also inhibits monoamine oxidase (MAO) and serotonin transporter (SERT). Studies conducted with [H3]pinoline have revealed high specific binding to nuclei of cells in the cerebral cortex and adrenal gland, suggesting a plausible effect at this organelle level. In order to gain more knowledge about these intriguing molecules we have based our approach in the systematic study of their pharmacological profiles (5-HTR, SERT, MAO, MT1/MT2, ORAC, AChE). Furthermore we have extended our efforts to the synthesis and evaluation of additional structures resulting from the merging of both pineal neurochemicals. So far, we have been able to determine that pinoline is a rather potent (EC50 = 33 nM) full agonist at the 5-HT2C which is in agreement with the role this receptor subtype displays in the sleeping homeostasis. Moreover we have been able to identify compound 1, as a potent in vitro neurogenic compound (Tuj+) able to promote neural maturity (MAP+) to a higher extent than melatonin. Being totally devoid of any affinity for the neurogenic 5-HTRs and unlikely to have any for MT1/MT2 receptors we are currently conducting studies to establish whether nuclear receptors could be implied in its neurogenic effect.
DescriptionResumen de la comunicacion oral presentada al XVII National Meeting of SEQT: "Advances in Drug Discovery: Successes, Trends and Future Challenges" celebrado en Madrid (España) del 2 al 4 de octubre de 2013.-- et al.
Appears in Collections:(IIBM) Comunicaciones congresos
(IQM) Comunicaciones congresos
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