Incorporation of an SRI (serotonin reuptake inhibitor) pharmacophore into a selective 5-HT(1D) agonist has led to the discovery of a molecule having both 5-HT(1D) antagonist and SRI activity. RPS methodology was used to develop the SAR and identify potential approaches to reduce unwanted adrenergic alpha 1 and dopamine D(2) cross-reactivities.
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http://dx.doi.org/10.1016/j.bmcl.2004.03.003 | DOI Listing |
Br J Pharmacol
February 2025
Laboratorio de Farmacología. Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.
Background And Purpose: In male rats, the serotonergic system modulates sympathetic outflow at vascular levels, causing sympatho-inhibition and sympatho-excitation, mainly via 5-HT and 5-HT receptors, respectively. However, sex influence on vascular serotonergic regulation has not yet been elucidated. This study aimed to analyse the 5-HT sympatho-modulatory role in female rats, characterising the 5-HT receptors involved.
View Article and Find Full Text PDFMol Pharmacol
May 2022
Department of Anesthesiology and Perioperative Medicine (L.A., V.R.-V.) and Heart and Vascular Institute (J.S.K., M.P.K.), Penn State College of Medicine, Hershey, Pennsylvania; and Department of Public Health Sciences Division of Biostatistics and Bioinformatics, Penn State Cancer Institute, Next-Generation Therapies, Hershey, Pennsylvania (S.Z.)
Serotonin (5-HT) is a multifaceted neurotransmitter that has been described to play a role as a peripheral inflammatory mediator when released in ischemic or injured muscle. Dorsal root ganglia (DRG) neurons are key sensors of noxious stimuli that are released under inflammatory conditions or mechanical stress. Little information is available on the specific 5-HT receptor subtypes expressed in primary afferents that help regulate reflex pressor responses.
View Article and Find Full Text PDFJ Headache Pain
February 2022
Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet Glostrup, 2600, Glostrup, Denmark.
Background: 5-Hydroxytryptamine (5-HT) receptors 1B, 1D and 1F have key roles in migraine pharmacotherapy. Selective agonists targeting these receptors, such as triptans and ditans, are effective in aborting acute migraine attacks and inhibit the in vivo release of calcitonin gene-related peptide (CGRP) in human and animal models. The study aimed to examine the localization, genetic expression and functional aspects of 5- HT receptors in the trigeminal system in order to further understand the molecular sites of action of triptans (5-HT) and ditans (5-HT).
View Article and Find Full Text PDFTher Adv Psychopharmacol
September 2021
Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy.
Chronic neuropathic pain (CNP) is a disabling medical condition that impairs the health-related quality-of-life of affected patients. A high prevalence of anxiety, depression, sleep disturbance and cognitive impairment has frequently been reported in association with CNP, making the management of this disease complex and often multidisciplinary. Dual-acting agents such as selective serotonin and noradrenalin reuptake inhibitors (SNRIs) are considered particularly useful in the modulation of pain and in treatment of the mood disorders frequently associated with CNP.
View Article and Find Full Text PDFProg Brain Res
July 2021
Department of Neurology, Kuang Tien General Hospital, Taichung, Taiwan; Department of Nutrition, Huang-Kuang University, Taichung, Taiwan. Electronic address:
Migraine is a common and highly disabling headache disorder associated with a substantial socioeconomic burden. Migraine treatments can be categorized as preventive treatment, aimed at reducing the frequency and severity of migraine attacks, and acute therapy, intended to abort attacks. Traditionally, acute treatment can be classified as specific (ergot derivatives and triptans) or nonspecific (analgesics and nonsteroidal anti-inflammatory drugs).
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