Browsing by Author "Reyes-Parada, Miguel"

Now showing 1 - 6 of 6
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    2-Arylthiomorpholine derivatives as potent and selective monoamine oxidase B inhibitors
    (2010) Luhr, Susan; Vilches-Herrera, Marcelo; Fierro Huerta, Angélica; Ramsay, Rona R.; Edmondson, Dale E.; Reyes-Parada, Miguel; Cassels, Bruce K.; Iturriaga-Vasquez, Patricio
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    3D similarities between the binding sites of monoaminergic target proteins
    (2018) Nunez-Vivanco, Gabriel; Fierro Huerta, Angélica; Moya, Pablo; Iturriaga-Vasquez, Patricio; Reyes-Parada, Miguel
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    Characterization of a Novel Drosophila SERT Mutant: Insights on the Contribution of the Serotonin Neural System to Behaviors
    (2017) Hidalgo, Sergio; Molina-Mateo, Daniela; Escobedo, Pia; Zarate, Rafaella V.; Fritz, Elsa; Fierro, Angelica; Perez, Edwin G.; Iturriaga-Vasquez, Patricio; Reyes-Parada, Miguel; Varas, Rodrigo; Fuenzalida-Uribe, Nicolas; Campusano, Jorge M.
    A better comprehension on how different molecular components of the serotonergic system contribute to the adequate regulation of behaviors in animals is essential in the interpretation on how they are involved in neuropsychiatric and pathological disorders. It is possible to study these components in "simpler" animal models including the fly Drosophila melanogaster, given that most of the components of the serotonergic system are conserved between vertebrates and invertebrates. Here we decided to advance our understanding on how the serotonin plasma membrane transporter (SERT) contributes to serotonergic neurotransmission and behaviors in Drosophila. In doing this, we characterized for the first time a mutant for Drosophila SERT (dSERT) and additionally used a highly selective serotonin-releasing drug, 4-methylthioamphetamine (4-MTA), whose mechanism of action involves the SERT protein. Our results show that dSERT mutant animals exhibit an increased survival rate in stress conditions, increased basal motor behavior, and decreased levels in an anxiety-related parameter, centrophobism. We also show that 4-MTA increases the negative chemotaxis toward a strong aversive odorant, benzaldehyde. Our neurochemical data suggest that this effect is mediated by dSERT and depends on the 4-MTA-increased release of serotonin in the fly brain. Our in silico data support the idea that these effects are explained by specific interactions between 4-MTA and dSERT. In sum, our neurochemical, in silico, and behavioral analyses demonstrate the critical importance of the serotonergic system and particularly dSERT functioning in modulating several behaviors in Drosophila.
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    Human and rat monoamine oxidase-A are differentially inhibited by (S)-4-alkylthioamphetamine derivatives: Insights from molecular modeling studies
    (2007) Fierro Huerta, Angélica; Osorio-Olivares, Mauricio; Cassels, Bruce K.; Edmondson, Dale E.; Sepulveda-Boza, Silvia; Reyes-Parada, Miguel
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    Improving Amphetamine Therapeutic Selectivity: N,N-dimethyl-MTA has Dopaminergic Effects and does not Produce Aortic Contraction
    (2014) Sotomayor-Zarate, Ramon; Jara, Pablo; Araos, Patricio; Vinet, Raul; Quiroz, Gabriel; Renard, Georgina M.; Espinosa, Pedro; Hurtado-Guzman, Claudio; Moya, Pablo R.; Iturriaga-Vasquez, Patricio; Gysling, Katia; Reyes-Parada, Miguel
    Amphetamine derivatives have therapeutic potential in diseases such as attention deficit hyperactivity disorder, narcolepsy and obesity. However, their prolonged use has been associated with cardiovascular toxicity and addiction. In recent years, we have studied the pharmacological effects of amphetamine derivatives such as methylthioamphetamine (MTA) and N,N-dimethyl-thioamphetamine, with the aim of improving their therapeutic selectivity. In this work, we show that similarly to MTA, N,N-dimethyl-thioamphetamine has effects on the dopamine system, producing a significant increase in extracellular levels of dopamine (as measured by in vivo brain microdialysis) and locomotor activity, which is a behavioural measure of dopaminergic activation. However, unlike MTA, N,N-dimethyl- thioamphetamine does not produce aortic contraction in vitro. Our results show that N,N-dimethyl-thioamphetamine is a drug that retains the dopaminergic effects of amphetamine derivatives but exhibits a lower potential for producing cardiovascular side effects.
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    Synthesis, docking and pharmacological evaluation of novel homo- and hetero-bis 3-piperazinylpropylindole derivatives at SERT and 5-HT1A receptor
    (2013) Pessoa-Mahana, Hernan; Gonzalez-Lira, Christian; Fierro, Angelica; Zapata-Torres, Gerald; David Pessoa-Mahana, C.; Ortiz-Severin, Javiera; Iturriaga-Vasquez, Patricio; Reyes-Parada, Miguel; Silva-Matus, Paul; Saitz-Barria, Claudio; Araya-Maturana, Ramiro
    A series of 3-(3-(4-(3-(1H-indol-3-yl)propyl)piperazin-1-yl)propyl)-1H-indole derivatives (3a-d and 5a-f) as homo-and hetero-bis-ligands, were synthesized and evaluated for in vitro affinity at the serotonin transporter (SERT) and the 5-HT1A receptor. Compounds 5b and 5f showed nanomolar affinities for both targets. The experimental data were rationalized according to results obtained from docking experiments. These findings are in agreement with our proposal that bis-indole derivatives can bind both targets, and might serve as leads in the quest of ligands endowed with a dual mechanism of action. (C) 2013 Elsevier Ltd. All rights reserved.