Browsing by Author "Quiroz, Gabriel"

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    4-Methylthioamphetamine Increases Dopamine in the Rat Striatum and has Rewarding Effects In Vivo
    (2012) Sotomayor Zárate, Ramón Eduardo; Quiroz, Gabriel; Araya Gutiérrez, Katherine Angélica; Abarca, Jorge; Ibañez, Maria R.; Montecinos, Alejandro; Guajardo, Carlos; Nuñez, Gabriel; Fierro Huerta, Angélica; Moya, Pablo R.; Iturriaga-Vasquez, Patricio; Gomez-Molina, Cristobal; Gysling Caselli, Katia
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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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    Necroptosis inhibition counteracts neurodegeneration, memory decline, and key hallmarks of aging, promoting brain rejuvenation
    (2023) Arrazola, Macarena S.; Lira, Matias; Veliz-Valverde, Felipe; Quiroz, Gabriel; Iqbal, Somya; Eaton, Samantha L.; Lamont, Douglas J.; Huerta, Hernan; Ureta, Gonzalo; Bernales, Sebastian; Cardenas, J. Cesar; Cerpa, Waldo; Wishart, Thomas M.; Court, Felipe A.
    Age is the main risk factor for the development of neurodegenerative diseases. In the aged brain, axonal degeneration is an early pathological event, preceding neuronal dysfunction, and cognitive disabilities in humans, primates, rodents, and invertebrates. Necroptosis mediates degeneration of injured axons, but whether necroptosis triggers neurodegeneration and cognitive impairment along aging is unknown. Here, we show that the loss of the necroptotic effector Mlkl was sufficient to delay age-associated axonal degeneration and neuroinflammation, protecting against decreased synaptic transmission and memory decline in aged mice. Moreover, short-term pharmacologic inhibition of necroptosis targeting RIPK3 in aged mice, reverted structural and functional hippocampal impairment, both at the electrophysiological and behavioral level. Finally, a quantitative proteomic analysis revealed that necroptosis inhibition leads to an overall improvement of the aged hippocampal proteome, including a subclass of molecular biofunctions associated with brain rejuvenation, such as long-term potentiation and synaptic plasticity. Our results demonstrate that necroptosis contributes to age-dependent brain degeneration, disturbing hippocampal neuronal connectivity, and cognitive function. Therefore, necroptosis inhibition constitutes a potential geroprotective strategy to treat age-related disabilities associated with memory impairment and cognitive decline.
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    Synthesis and docking of novel 3-indolylpropyl derivatives as new polypharmacological agents displaying affinity for 5-HT1AR/SERT
    (2016) Pessoa Mahana, Hernán; Silva Matus, Paul; Pessoa Mahana, Carlos David; Chung, Hery; Iturriaga Vásquez, Patricio; Quiroz, Gabriel; Möller Acuña, Patricia; Zapata Torres, Gerald; Saitz Barría, Claudio Antonio; Araya Maturana, Ramiro; Reyes Parada, Miguel