Pharmacological Interaction of Quercetin Derivatives of Tilia americana and Clinical Drugs in Experimental Fibromyalgia.

Fibromyalgia (FM) is a pain syndrome characterized by chronic widespread pain and CNS comorbidities. Tilia americana var. mexicana is a medicinal species used to treat anxiety, insomnia, and acute or chronic pain. However, its spectrum of analgesic efficacy for dysfunctional pain is unknown. To investigate a possible therapeutic alternative for FM-type pain, an aqueous Tilia extract (TE) and its flavonoid fraction (FF) containing rutin and isoquercitrin were evaluated alone and/or combined with clinical drugs (tramadol-TRA and pramipexol-PRA) using the reserpine-induced FM model in rats. Chromatographic analysis allowed the characterization of flavonoids, while a histological analysis confirmed their presence in the brain. TE (10-100 mg/kg, i.p.) and FF (10-300 mg/kg, i.p.) produced significant and dose-dependent antihyperalgesic and antiallodynic effects equivalent to TRA (3-10 mg/kg, i.p.) or PRA (0.01-1 mg/kg, s.c.). Nevertheless, the combination of FF + TRA or FF + PRA resulted in an antagonistic interaction by possible competitive action on the serotonin transporter or µ-opioid and D2 receptors, respectively, according to the in silico analysis. Flavonoids were identified in cerebral regions because of their self-epifluorescence. In conclusion, Tilia possesses potential properties to relieve FM-type pain. However, the consumption of this plant or flavonoids such as quercetin derivatives in combination with analgesic drugs might reduce their individual benefits.

Mirtazapine impairs acquisition and reinstatement of cocaine-induced place preference in rats.

Exposure to cues previously associated with drug use and the environment can trigger intense craving and drug-seeking, often leading to relapse in individuals with substance use disorders. Several studies suggest that the decrease in the effects of the cues and the environment could help maintain abstinence from drug use in individuals abusing drugs. Mirtazapine, an antagonist of the noradrenergic (NE) α2 receptor and the 5-HT2A/C and 5-HT3 receptors has demonstrated efficacy in reducing the rewarding effect of different drugs. The purpose of the present study was to investigate whether the mirtazapine, blocks the acquisition and reinstatement of cocaine-induced conditioned place preference (CPP). In this study, 120 Wistar male rats were utilized and we use the CPP as a behavioral tool to measure the context-rewarding effect of an unconditioned stimulus such as cocaine. Mirtazapine was dosed for 30 or 60 consecutive days prior to treatment with cocaine or during the extinction phase. We found that dosing with mirtazapine for 30 consecutive days caused a time-related reduction in acquisition or reinstatement of preference for the cocaine-paired chamber. When the duration of treatment is increased (60 days), reductions in preference for the cocaine-paired chamber were potentiated. These observations support its potential clinical anti-addictive properties against drugs.

Nuevas vacunas contra la morfina/heroína / Novel Vaccines against morphine/heroin

Drug addiction is one of the most important health problems in the world. This psychiatry disease results in the death of about 500 000 individuals annually in the world. Despite this scenario, the development of effective drug therapies against this disease has been slow and not very successful. In recent years, new alternative pharmacological strategies against drug addiction have been designed and validated. Among them are vaccines against drugs like nicotine, morphine or cocaine and their subsequent use in immunotherapeutic pharmacological procedures for the treatment of addictive behaviors of drug consumption, both in animal models and in humans. These strategies are based on the experimental design and synthesis of various structural formulations of therapeutic vaccines against drugs of abuse. When dosed in active immunization schedules, they induce the production of specific antibodies, which recognize and bind these substances in the intravascular space and prevent the drug permeability through the blood brain barrier, resulting in decreased effects of drugs into the brain. In 2006, our research group at the National Institute of Psychiatry Ramón de la Fuente Muñiz (INPRFM) achieved and consolidated the design, synthesis, application and validation of immunoprotective therapeutic effects against relapse to morphine/heroin addiction in a rodent animal model, a model vaccine for potential human use against addiction to morphine/heroin. This model shows immunogenic capacities (high and sustained titers of highly specific antibodies) and immunoprotection (attenuates the effect up to 15mg/kg sc morphine) that the structural vaccine models competing have not been matched, which makes it the leading vaccine model against the addictive effects of heroin and morphine.

La adicción a una droga de abuso representa uno de los problemas sanitarios más importantes ya que esta patología genera la muerte de cerca de 500 000 sujetos anualmente en el mundo. A pesar de este panorama, el desarrollo de terapias farmacológicas efectivas contra esta enfermedad es lento y poco exitoso. En los últimos años se han diseñado y validado nuevas estrategias farmacológicas alternativas contra la adicción a drogas de abuso, como las vacunas y su uso en procedimientos farmacológicos inmunoterapéuticos para el tratamiento de esas conductas tanto en modelos de animales como en el humano. Estas nuevas estrategias experimentales están basadas en el diseño y síntesis de diversas formulaciones estructurales de vacunas terapéuticas contra las sustancias de abuso las cuales, al ser dosificadas en esquemas de inmunización activa, inducen la producción de anticuerpos séricos específicos que reconocen y se unen a estas sustancias en el espacio intravascular sistémico e impiden que crucen la barrera hematoencefálica, con lo cual disminuyen sus efectos en el cerebro. En el año 2006 nuestro grupo de trabajo en el Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz (INPRFM) logró y consolidó el diseño, síntesis, aplicación y validación de efectos terapéuticos inmunoprotectores contra recaídas al consumo adictivo de morfina/heroína, en un modelo animal con roedores y su escalamiento potencial para uso humano contra la adicción a esas sustancias. Este modelo muestra capacidades inmunogénicas (títulos altos y sostenidos de anticuerpos altamente específicos) y de inmunoprotección (atenúa el efecto de hasta 15mg/Kg sc de morfina) que los modelos estructurales de vacuna desarrollados por otros grupos de investigadores no han podido igualar. Esto lo convierte en un modelo líder de vacuna contra los efectos adictivos de la heroína y morfina.