Sumatriptan attenuates fear-learning despair induced by social isolation stress in mice: Mediating role of hypothalamic-pituitary-adrenal axis.

OBJECTIVES: Research has demonstrated that chronic stress experienced early in life can lead to impairments in memory and learning. These deficits are attributed to an imbalance in the interaction between glucocorticoids, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, and glucocorticoid receptors in brain regions responsible for mediating memory, such as the hippocampus. This imbalance can result in detrimental conditions like neuroinflammation. The aim of this study was to assess the impact of sumatriptan, a selective agonist for 5-HT 1B/1D receptors, on fear learning capabilities in a chronic social isolation stress model in mice, with a particular focus on the role of the HPA axis. METHODS: Mice were assigned to two opposing conditions, including social condition (SC) and isolated condition (IC) for a duration of five weeks. All mice underwent passive avoidance test, with their subsequent freezing behavior serving as an indicator of fear retrieval. Mice in the IC group were administered either a vehicle, sumatriptan, GR-127935 (a selective antagonist for 5-HT 1B/1D receptors), or a combination of sumatriptan and GR-127935 during the testing sessions. At the end, all mice were sacrificed and samples of their serum and hippocampus were collected for further analysis. RESULTS: Isolation was found to significantly reduce freezing behavior (p<0.001). An increase in the freezing response among IC mice was observed following the administration of varying doses of sumatriptan, as indicated by a one-way ANOVA analysis (p<0.001). However, the mitigating effects of sumatriptan were reversed upon the administration of GR-127935. An ELISA assay conducted before and after the passive avoidance test revealed no significant change in serum corticosterone levels among SC mice. In contrast, a significant increase was observed among IC mice, suggesting hyper-responsiveness of the HPA axis in isolated animals. This hyper-responsiveness was ameliorated following the administration of sumatriptan. Furthermore, both the sumatriptan and SC groups exhibited a similar trend, showing a significant increase in the expression of hippocampal glucocorticoid receptors following the stress of the passive avoidance test. Lastly, the elevated production of inflammatory cytokines (TNF-α, IL-1ß) observed following social isolation was attenuated in the sumatriptan group. CONCLUSION: Sumatriptan improved fear learning probably through modulation of HPA axis and hippocampus neuroinflammation.

Sumatriptan mitigates bleomycin-induced lung fibrosis in male rats: Involvement of inflammation, oxidative stress and α-SMA.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung condition that produces symptoms including coughing which may cause by excessive accumulation of scar tissue inflammatory and oxidative stress exacerbation. Sumatriptan, utilized for migraine treatment as a selective 5-HT1B/1D receptor agonist, has demonstrated significant anti-inflammatory and antioxidant properties in multiple preclinical investigations. Operating primarily on serotonin receptors, sumatriptan leverages the diverse physiological functions of serotonin, playing a pivotal role in regulating both inflammation and oxidative stress which is particularly relevant in the context of IPF. MATERIALS & METHODS: Thirty-five male Wistar rats were divided to five group, including: Sham (without IPF induction), control (BLM 5 mg/kg, intraperitoneally), and three fibrosis group with sumatriptan (0.5, 1, and 3 mg/kg, i.p. for 2 weeks) administration. IPF was induced by injection of BLM (single dose, 5 mg/kg intratracheally). Lung tissues were separated for measurement of myeloperoxidase (MPO) as an oxidative stress hallmark, and tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-ß), and transforming growth factor-ß (TGF-ß) as inflammatory markers as well as alpha smooth muscle actin (α-SMA). Also, for histological investigations, tissue damages were assessed by Hematoxylin-eosin (H&E) and Masson's trichrome staining method. RESULTS: BLM-induced fibrosis could increase α-SMA, MPO, TNF-α, IL-1ß, and TGF-ß, while treatment with sumatriptan has reversed the α-SMA, MPO, and IL-1ß levels. Moreover, the results of H&E and Masson's trichrome staining indicated that sumatriptan (1 and 3 mg/kg) reduced tissue damages, alveolar wall thickness, collagen accumulation, and pulmonary fibrosis induced by BLM. CONCLUSION: According to the data achieved from this study, Sumatriptan appears to have therapeutic benefits in IPF, possibly via reducing α-SMA as well as inflammation and the toxicity caused by oxidative stress.

Pharmacology of erenumab in human isolated coronary and meningeal arteries: Additional effect of gepants on top of a maximum effect of erenumab.

BACKGROUND AND PURPOSE: Multiple drugs targeting the calcitonin gene-related peptide (CGRP) receptor have been developed for migraine treatment. Here, the effect of the monoclonal antibody erenumab on CGRP-induced vasorelaxation was investigated in human isolated blood vessels, as well as the effect of combining erenumab with the small molecule drugs, namely rimegepant, olcegepant, or sumatriptan. EXPERIMENTAL APPROACH: Concentration-response curves to CGRP, adrenomedullin or pramlintide were constructed in human coronary artery (HCA) and human middle meningeal artery (HMMA) segments, incubated with or without erenumab and/or olcegepant. pA2 or pKb values were calculated to determine the potency of erenumab in both tissues. To study whether acutely acting antimigraine drugs exerted additional CGRP-blocking effects on top of erenumab, HCA segments were incubated with a maximally effective concentration of erenumab (3 µM), precontracted with KCl and exposed to CGRP, followed by rimegepant, olcegepant, or sumatriptan in increasing concentrations. KEY RESULTS: Erenumab shifted the concentration-response curve to CGRP in both vascular tissues. However, in HCA, the Schild plot slope was significantly smaller than unity, whereas this was not the case in HMMA, indicating different CGRP receptor mechanisms in these tissues. In HCA, rimegepant, olcegepant and sumatriptan exerted additional effects on CGRP on top of a maximal effect of erenumab. CONCLUSIONS AND IMPLICATIONS: Gepants have additional effects on top of erenumab for CGRP-induced relaxation and could be effective in treating migraine attacks in patients already using erenumab as prophylaxis.

Palatal myoclonus: report of two cases

We describe two cases of palatal myoclonus (PM), one essential and another secondary to a stroke. Case 1: a 64 years old female who developed clicking sounds in both ears after a stroke and three years later on noticed a progressive involuntary movement of the throat associated with rhythmic contractions of the soft palate, muscles of tongue and throat. MRI showed an ischemic area in brainstem. The patient had a partial response to the use of sumatriptan 6 mg subcutaneously. Case 2: a 66 years old female who began with ear clicking at left ear that worsed slowly associated with tinnitus and arrhythmic movements of soft palate and an audible click at left ear. Brain MRI was normal; audiometry showed bilateral neurosensory loss. She was prescribed clonazepan 1 mg daily with complete recovery. Primary and secondary palatal myoclonus share the same clinical features but probably have different pathophysiological underlying mechanisms

Método HPLC para la determinación del sumatriptán en plasma y tejido cerebral / HPLC method for the determination of sumatriptan in plasma and brain tissue

Se ha desarrollado un método de cromatografía de líquidos de alto rendimiento ultravioleta sensible y rápido y se ha validado para la determinación del sumatriptán, un agonista de serotonina, en muestras de homogeneizado de cerebro y plasma de rata. Una vez realizada una extracción líquido-líquido de sumatriptán y ofl oxacina (estándar interno), los compuestos se separaron en una columna de fase inversa C-18, eluida con un 22% de acetonitrilo y un 78% de tampón fosfato amónico (0,04 M, PH ajustado 3,7) y detectada a 228 nm. Este método muestra una buena linealidad para las muestras de plasma y tejido cerebral con un rango de concentración muy amplio de 3–2000 ng/ml y 3-1000 ng/g respectivamente, y un coefi ciente de correlación de 0,9998 y 0,9994. Con este método se obtuvieron buenos resultados de precisión (CV interdía e intradía < 9,1%) y exactitud (margen de error interdía e intradía < 7,3%). El límite de la concentración de cuantifi cación fue 3 de ng/ml. La recuperación absoluta del sumatriptán fue superior al 93,4% para el plasma y al 89,5% para las muestras de tejido cerebral. Este método es sencillo, rápido y sensible. El método propuesto podría resultar ventajoso en la estimación del sumatriptán incorporado en sistemas de administración que concentran el fármaco en plasma y en muestras de tejido cerebral y se podría utilizar en estudios farmacocinéticos en modelos animales

A rapid and sensitive ultra-violet high-performance liquid chromatographic method was developed and validated for the determination of sumatriptan, a serotonin agonist in rat plasma and brain homogenate samples. After a liquid–liquid extraction of sumatriptan and ofl oxacin (internal standard) , the compounds were separated on a reversed-phase C-18 column, eluted with 22% of acetonitrile and 78% of ammonium phosphate buffer (0.04 M, adjusted pH 3.7) and detected at 228 nm. This method shows a good linearity for plasma and brain samples with very wide concentration range of 3–2000 ng/ml and 3-1000 ng/g respectively, and correlation coeffi cient of 0.9998 and 0.9994. A good precision (inter and intra day CV < 9.1%) and a good accuracy (inter and intra day bias < 7.3%) was obtained with this method. The limit of quantifi cation concentration was 3 ng/ml. The absolute recovery of sumatriptan was higher than 93.4% for plasma and 89.5% for brain samples. This method is simple, rapid and sensitive. The proposed method could be advantageous in estimation of sumatriptan incorporated into delivery systems that concentrate drug in plasma as well as brain tissues and could be used for pharmacokinetics studies in animal model

O sumatriptano no tratamento da crise de enxaqueca / Using Sumatriptan to treat headache

A cefaléia é um dos sintomas mais comuns da clínica médica tanto em adultos como em crianças. Dos pacientes que procuram atendimento médico pela queixa de cefaléia, em aproximadamente um quarto é feito o diagnóstico de enxaqueca segundo os critérios da International Headache Society (IHS) de 1988. Feito o diagnóstico de exaqueca, a terapêutica tem como base a intensidade da crise. Nas crises de leve à moderada intensidade se orienta ao paciente repouso e uso de analgésicos comuns (tipo AAS), e nos casos mais resistentes o uso de antiinflamatórios näo-esteróide (AINES). Nas crises de moderada à severa intensidade está indicado o uso de derivados do ergot e, mais recentemente, o sumatriptano, um agonista dos receptores 5-HT1D, como alternativa eficaz e relativamente segura. No presente artigo é apresentada uma revisäo acerca do uso do sumatriptano no tratamento das crises de enxaqueca e, em especial, dos seus aspectos farmacológicos

Tratamientos farmacológicos para la migraña aguda: revisión sistemática cuantitativa / Pharmacological treatments for acute migraine: quantitative systematic review

La finalidad de este estudio fue comparar la eficacia analgésica y los efectos adversos de los tratamientos farmacológicos para la migraña aguda por medio de una revisión sistemática de estudios aleatorizados y controlados en pacientes con dolor por migraña aguda de intensidad moderada o severa. Los estudios se localizaron mediante una búsqueda sistemática de bases de datos bibliográficas. Pfizer Inc. proporcionó información sobre todos los estudios realizados con eletriptán. Los resultados considerados fueron el alivio del dolor de cabeza al cabo de 1 y 2 horas, la ausencia de dolor en los pacientes a las 2 horas y el alivio sostenido durante 24 horas con los tratamientos comparados con placebo. Se calculó el número necesario de tratamientos (NNT) y el beneficio relativo. Se recogió también información sobre los efectos adversos. Las comparaciones de la eficacia relativa utilizaron la misma definición de dolor de cabeza, el mismo grado de dolor al inicio del tratamiento y las mismas definiciones de los resultados, y siempre se compararon con placebo. En los metaanálisis se incluyeron 48 publicaciones referidas a 54 estudios, y se realizaron 79 comparaciones frente a placebo para el principal resultado considerado: el alivio del dolor de cabeza al cabo de 2 horas. Se dispuso de información sobre todos los resultados de nueve medicaciones orales, dos medicaciones intranasales y sumatriptán subcutáneo en 21.022 pacientes. Para el alivio del dolor de cabeza al cabo de 2 horas, el NNT varió entre 2,0 para el sumatriptán subcutáneo 6 mg y 5,4 para el naratriptán 2,5 mg. En los pacientes sin dolor al cabo de 2 horas, el NNT varió entre 2,1 para el sumatriptán subcutáneo 6 mg y 8,6 para la aspirina 900 mg más metoclopramida 10 mg. En los pacientes con alivio sostenido del dolor durante 24 horas, el NNT varió entre 2,8 para el eletriptán 80 mg y 8,3 para el rizatriptán 5 mg. No fue posible realizar una revisión sistemática de los datos sobre efectos adversos. La mayor parte de las intervenciones fueron eficaces. Existe un volumen considerable de información sobre la eficacia relativa para una serie de resultados (AU)

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¿Demasiados triptanes para el tratamiento de la migraña? / Too much triptans for the management of migraine?

En los últimos años, se han venido introduciendo progresivamente en el mercado farmacéutico español diversos agentes pertenecientes al grupo de agonistas r de la serotonina (5 HT1) para el tratamiento de la migraña, que constituyen una nueva clase de medicamentos también conocidos como triptanes. Sumatriptan, fue el primero comercializado, incorporándose después almotriptan, eletriptan, naratriptan, rizatriptan y zolmitriptan. El presente artículo tiene como objetivo revisar la información disponible sobre estos nuevos agentes, establecer a la luz de las evidencias disponibles sus potenciales ventajas e inconvenientes; y, de acuerdo con los estudios realizados y de la experiencia disponible, valorar su papel en la terapéutica de la migraña (AU)

Eficacia de la PGE1 en el tratamiento de la intoxicación crónica por ergotamina / Effectiveness of PGE1 for the treatment of chronic poisoning byergotamine

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