Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

¿Regresa la tan vilipendiada reserpina? / Is the so contemned reserpine back?

Se hizo una revisión de los ensayos clínicos recientes que emplearon reserpina a dosis menores o iguales a 0,25 mg/diarios con el propósito de determinar si a estas dosis puede ser eficaz y bien tolerada. Se analizaron las causas que han llevado a una disminución de su prescripción a pesar de haber reducido significativamente las complicaciones derivadas de la hipertensión arterial. En un análisis de costos, comparado con otros antihipertensivos, demostró ser el más barato. Se concluye que las características de: eficacia, buena tolerancia, duración de acción y bajo costo a dosis menores de 0,25 mg hacen que deba considerarse su empleo como fármaco de primera elección en el tratamiento de la hipertensión arterial primaria, administrada sola o en combinación con dosis, también bajas, de diuréticos tiacídicos

Efeitos do bloqueio simpático na hipertrofia cardíaca após infarto e suas repercussöes na contratilidade miocárdica / Effects of sympathetic block on post-infarction cardiac hypertrophy and their repercussion on myocardial contractility

Objetivo Investigar os efeitos do uso crônico de reserpina (Res) ou propranolol (Prop), administrados subcutaneamente, na evolução da hipertrofia cardíaca e contratilidade miocárdica após infarto do miocárdio (IM). Métodos Ratos albinos com 3 meses de idade foram submetidos à ligadura dos ramos anteriores da artéria coronária esquerda para a produção de IM. Ratos submetidos a cirurgia fictícia foram usados como grupo controle. Os animais tratados com Res (0,5 mg/kp/dia) foram sacrificados 8-10 dias após a cirurgia e os tratados com Prop (2,5 mg/kg a cada 12h) foram sacrificados 15 (G-15) ou 30 (G-30) dias após. A hipertrofia foi avaliada pelo peso das câmaras cardíacas, corrigido para o peso corporal. A contratilidade miocárdica foi medida através da força (F) desenvolvida por tiras isoladas do ventrículo direito (VD) contraindo-se isometricamente. Resultados A Res inibiu completamente a hipertrofia dos átrios e do VD. A extensão do IM, medida pelo perceptual de área do ventrículo esquerdo (VE) coberta pela cicatriz fibrosa, não foi afetada pelo Prop (32 ± 4% nos animais com IM tratados com solução salina e 30 ± 3% nos tratados com Prop). O Prop também inibiu significativamente a hipertrofia atrial e do VD. No G-30, por exremplo, os pesos relativos (mg/ g) do AD e VD foram menores (P < 0,05) nos animais com IM e tratados com Prop (0,12 ± 0,01 e 0,79 ± 0,07) que naqueles com IM tratados com solução salina (0,22 ± 0,03 e 1,11 ± 0,07). A F basal produzida nos músculos de corações com IM foi 25 a 30% menor que nos controles. Essa queda foi reduzida para apenas 4% (G-15) e 8% (G-30) nos músculos de animais com IM tratados com Prop treatment...

Purpose — To investigate the effects of chronical subcutaneous administration of reserpine (Res) or propranolol (Prop) on the postinfarction myocardial hypertrophy and the effects of Prop treatment on myocardial contractility in rats. Methods — Male albino rats (3-month-old) were submitted to left coronary artery ligation to produce myocardial infarction. Rats submitted to a sham-operation were used as controls. Animals submitted to Res (0.5 mg/Kg/day) were killed 8-10 days after surgery and those submitted to Prop (2.5 mp/kg twice a day) were killed 15 (G-15) or 30 (G-30) days later. Hypertrophy was evaluated according to cardiac chambers weight corrected to body weights. Isometric force (F) developed by isolated right ventricular (RV) strips was used as a contractile index. Results — Atrial and RV hypertrophy were completely blocked by Res. Prop treatment did not significantly change infarct extension, evaluated by the fibrous scar area. Prop therapy also reduced atrial and RV hypertrophy. This effect was less intense compared to Res, however. In the G-30, for example, the relative right atrial and RV weights (mp/g) were 0.10 ± 0.01 and 0.59 ± 0.03 in sham-operated animais (n = 9), 0.12 ± 0.01 and 0.079 ± 0.07 in infarcted animals with Prop (n = 11) and 0.22 ± 0.03 and 1.11 ± 0.07 in those infarcted and treated with saline solution (n = 11). Basal F values were 25 to 30% lower in RV strips from infarcted than in sham-operated hearts. This reduction however was only 4% (G-15) and 8% (G-30) in infarcted hearts under Prop treatment...