Bioisosterism and conformational restriction: ligand-based design in the development of nicotinic ligands and melatonin analogues with neurogenic properties

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Química Farmacéutica, leída el 15-09-2014Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaTRUEunpu

Compuestos neurogénicos basados en melatonina y su uso en el tratamiento de enfermedades del sistema nervioso

La presente invención, que se incluye en el campo de la investigación e industria farmacéutica, se refiere a nuevas entidades químicas derivadas de melatonina con propiedades neurogénicas, moduladoras de los receptores de melatonina y/o serotonina, antioxidantes y/o colinérgicas. También se refiere a los procedimientos para la preparación de estos nuevos compuestos, a las composiciones farmacéuticas que los contienen y a su uso para la fabricación de un medicamento para el tratamiento de enfermedades del sistema nervioso relacionadas con degeneración neuronal, depresión, trastornos psiquiátricos y cognitivos, trauma o lesión celular, u otro trastorno neurológico relacionado, tratamiento de fatiga diurna, trastornos del sueño, pérdida de eficacia mental, debilidad e irritabilidad y síntomas relacionados con la descompensación horaria (efecto jet-lag o síndrome transoceánico).Peer reviewedConsejo Superior de Investigaciones Científicas, Universidad Autónoma de MadridB1 Patente sin examen previ

Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking

INTRODUCTION: Ayahuasca is a South American psychotropic plant tea traditionally used in Amazonian shamanism. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine oxidase-inhibiting properties. Increasing evidence from anecdotal reports and open-label studies indicates that ayahuasca may have therapeutic effects in treatment of substance use disorders and depression. A recent study on the psychological effects of ayahuasca found that the tea reduces judgmental processing and inner reactivity, classic goals of mindfulness psychotherapy. Another psychological facet that could potentially be targeted by ayahuasca is creative divergent thinking. This mode of thinking can enhance and strengthen psychological flexibility by allowing individuals to generate new and effective cognitive, emotional, and behavioral strategies. The present study aimed to assess the potential effects of ayahuasca on creative thinking. METHODS: We visited two spiritual ayahuasca workshops and invited participants to conduct creativity tests before and during the acute effects of ayahuasca. In total, 26 participants consented. Creativity tests included the "pattern/line meanings test" (PLMT) and the "picture concept test" (PCT), both assessing divergent thinking and the latter also assessing convergent thinking. RESULTS: While no significant effects were found for the PLMT, ayahuasca intake significantly modified divergent and convergent thinking as measured by the PCT. While convergent thinking decreased after intake, divergent thinking increased. CONCLUSIONS: The present data indicate that ayahuasca enhances creative divergent thinking. They suggest that ayahuasca increases psychological flexibility, which may facilitate psychotherapeutic interventions and support clinical trial initiatives

Assessing the Psychedelic "After-Glow" in Ayahuasca Users : Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities

Ayahuasca is a plant tea containing the psychedelic 5-HT agonist N,N -dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures. Using 1 H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose. Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the "nonjudging" subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later. These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca

Mixing Console Control in an Embedded System

Iegulto sistēmu programmēšanai ir savas specifiskas problēmas un izaicinājumi. Skaņu pults vadības programmatūras izstrāde Freescale Coldfire MCF527x procesoram ir šāds izaicinājums. Kā uzrakstīt funkcionālu moduli šai programmai noteiktā termiņā? Radio skaņu pults vadības modulim jānodrošina lietotāja komandu apstrāde un pareiza reaģēšana uz tām. Jānodrošina saskarne gan ar parastu lietotāja pults moduli, gan ar specializētu telefonijas moduli. Izstrādē tiek izmantoti spējās programmatūras izstrādes paņēmieni. Programmētājam tiek doti labi rīki un rīcības brīvība. Lietojot spējo metodoloģiju un izmantojot aparatūras emulatorus, strādājošs kods tiek izveidots vismaz divreiz ātrāk nekā pareģots, pat apsteidzot pašas iekārtas izstrādi. Attīstību veicinošā vidē programmētājs spēj uzrakstīt strādājošu iegulto programmatūru.Embedded programming presents specific challenges. To make mixing console code on Freescale Coldfire MCF527x is one of these challenges. How to write a functional program module given strict time schedule for such a system? Radio mixing console user logic module must provide for correct processing of user commands. Interface must be provided not only to regular mixing console board, but also a specialized board, which is used with telephony products. Agile development approaches are to be used. Programmer must be given good tools and certain degree of freedom. Turns out, agile methodologies and hardware emulators allow production of working code twice as fast as conventional metrics would suggest, producing software ahead of hardware. Thus, given appropriately nurturing environment programmers do make reasonable embedded programs

The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro

Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic effect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres prepared from progenitor cells obtained from the subventricular and the subgranular zones of adult mice brains, all compounds stimulated neural stem cell proliferation, migration, and differentiation into adult neurons. These findings suggest that modulation of brain plasticity could be a major contribution to the antidepressant effects of ayahuasca. They also expand the potential application of B. caapi alkaloids to other brain disorders that may benefit from stimulation of endogenous neural precursor niches.This work was supported by the MINECO (Grants SAF2010-16365 and SAF2014-52940-R to A.P-C and grants SAF2012-31035 and SAF2015-64948-C2-1-R to M.I.R.-F.), and was partially financed with FEDER funds. J.R. received funding from the Beckley Foundation. CIBERNED is funded by the Instituto de Salud Carlos III. J.A.M-G. is a post-doctoral fellow from CIBERNEDPeer Reviewe

Compuestos neurogénicos basados en melatonina y su uso en el tratamiento de enfermedades del sistema nervioso

La presente invención, que se incluye en el campo de la investigación e industria farmacéutica, se refiere a nuevas entidades químicas derivadas de melatonina con propiedades neurogénicas, moduladoras de los receptores de melatonina y/o serotonina, antioxidantes y/o colinérgicas. También se refiere a los procedimientos para la preparación de estos nuevos compuestos, a las composiciones farmacéuticas que los contienen y a su uso para la fabricación de un medicamento para el tratamiento de enfermedades del sistema nervioso relacionadas con degeneración neuronal, depresión, trastornos psiquiátricos y cognitivos, trauma o lesión celular, u otro trastorno neurológico relacionado, tratamiento de fatiga diurna, trastornos del sueño, pérdida de eficacia mental, debilidad e irritabilidad y síntomas relacionados con la descompensación horaria (efecto jet-lag o síndrome transoceánico).Peer reviewedConsejo Superior de Investigaciones Científicas, Universidad Autónoma de MadridA1 Solicitud de patente con informe sobre el estado de la técnic