Salix · CHRM1 · Small Molecule
hyoscyamine sulfate is a small molecule developed by Salix. It is approved for therapeutic indications via oral (po) or sublingual (sl)/oral transmucosal.
| Brand Names | IBStat |
| Company | Salix |
| Drug Class | Small Molecule |
| Molecular Target | CHRM1, CHRM2, CHRM3, CHRM4 |
| Route | Oral (PO), Sublingual (SL)/Oral Transmucosal |
| Status | Approved |
hyoscyamine sulfate acts on 4 molecular targets:
| CHRM1 | cholinergic receptor muscarinic 1 (M1, HM1) |
| CHRM2 | cholinergic receptor muscarinic 2 (HM2) |
| CHRM3 | cholinergic receptor muscarinic 3 (HM3, PBS) |
| CHRM4 | cholinergic receptor muscarinic 4 (HM4, M4R) |
hyoscyamine sulfate is developed for 1 unique indication across 1 therapeutic area.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Gastrointestinal disorders | Irritable bowel syndrome | ✓ Approved |
Lan Haifeng H, Lu Mengjie M, Li Shupei S, Shao Mei M et al.
[This corrects the article DOI: 10.3389/fmed.2026.1696298.].
D'Angelo Grace G, Kleiner Manuel M, Mankowski Anna A, Cifuentes-Anticevic Jerónimo J et al.
Sulfate-reducing bacteria (SRB) are widespread in marine and terrestrial environments, where they often form syntrophic associations with bacteria, archaea, and eukaryotes. Among the most intimate of these are multipartite symbioses in gutless marine oligochaete worms, which host SRB and sulfur-oxidizing endosymbionts that engage in a syntrophic exchange of sulfur compounds. Despite decades of research on free-living SRB, the metabolic traits that enable SRB to persist in symbiosis, and how these differ across hosts and environments, remain poorly understood. We show that a globally distributed clade of symbiotic SRB, which we named Candidatus Desulfoconcordia, has a conserved core metabolism that diverges from free-living relatives. Using comparative genomics and metaproteomics, we reveal that these endosymbionts retain key traits of SRB such as sulfate reduction, complete oxidation of acetate to CO2, amino acid degradation for nitrogen acquisition, and transport of essential nutrients. However, they exhibit a more oxygen-tolerant metabolism and lack typical nutrient-scavenging mechanisms of free-living SRB. One trait, the glyoxylate bypass, was consistently expressed in situ and may serve both in reactive oxygen species defence and in biomass generation. The expression of oxygen-tolerant pathways, coupled with the loss of nutrient-scavenging functions, indicate specialization to a host-associated, redox-fluctuating environment distinct from that of free-living SRB. The symbiont genomes are also larger than those of free-living relatives, contrasting with genome reduction in many endosymbionts and reinforcing the importance of metabolic versatility. Our findings provide a framework for understanding how metabolic flexibility enables SRB to persist in long-term multipartite symbioses across diverse marine ecosystems.
Kamanga Martha M, Kapalamula Felister F, Kazembe Abigail A, Kabondo Charity C et al.
BackgroundPreeclampsia and eclampsia are major contributors to maternal mortality in Malawi. Magnesium sulfate (MgSO4) is recommended by the World Health Organisation for the treatment of eclampsia. Despite its inclusion in national guidelines, there are inconsistencies in its clinical application, reflecting potential gaps in provider competency within Emergency Obstetric and Neonatal Care (EmONC) settings.ObjectivesThis study evaluates the knowledge, skills, and confidence of EmONC providers regarding MgSO4 administration and identifies context-specific barriers to optimal practice.DesignA qualitative descriptive study using a Human-Centred Design (HCD) approach.MethodsData collection involved focus group discussions and participatory workshops with registered nurse-midwives, nurse-midwife technicians, clinical officers, and District Health Management team members from selected EmONC facilities in Malawi. Thematic analysis based on Braun and Clarke's framework identified competency gaps and systemic barriers.ResultsThree interrelated gaps emerged: (1) fragmented knowledge of MgSO4 protocols, especially on maintenance dosing and toxicity; (2) inconsistent performance in drug preparation and administration; and (3) low psychological readiness among junior staff due to fear of complications and limited mentorship. System-level barriers included inadequate simulation-based training and a lack of visual job aids. HCD sessions led to co-created solutions, such as laminated dosage charts and peer-led simulations.ConclusionSignificant individual and systemic challenges exist in MgSO4 administration within EmONC settings. Enhancing provider competency through simulation-based learning, targeted mentorship, and visual decision-support tools could improve emergency care responses.
Yang Liping L, Gao Bingling B, Yang Tao T, Tang Liping L et al.
Dehydroepiandrosterone sulfate (DHEAS), a crucial steroid hormone for adrenal function and pubertal development, is highly associated with related diseases. This study aims to develop and validate an isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (cRMP) for quantifying serum DHEAS. Serum samples were prepared by protein precipitation with acetonitrile and separated on a reversed phase column. Assay validation was conducted under the guidance of standard documents, including C62-A, EP6-A, EP10-A3, and C50-P endorsed by the Clinical and Laboratory Standards Institute (CLSI). The cRMP was established and proven to be highly specific without significant matrix effect and able to accurately quantify DHEAS in human serum. The intra-assay and inter-assay imprecision ranged from < 0.1 to 1.0% and from 1.0 to 1.1%, respectively. Trueness was assessed by recovery rate from 99.6 to 101.2%. The limit of detection (LoD) was 0.270 nmol/L, and the lower limit of the measuring interval (LLMI) was 12.1 nmol/L. A linear correlation ranged from 7.60 to 41 858 nmol/L was observed with a correlation coefficient > 0.999. R2 value of linear regression analysis between this method and clinical immunoassays was ≥ 0.990. The relative expanded uncertainty was 1.5%-2.5% over the concentration range of 12.1-33 043 nmol/L. This study developed an ID-LC-MS/MS-based cRMP, which provided high specificity, trueness, and precision for serum DHEAS quantification, contributing to the DHEAS measurement standardization and traceability.
Yao Shuge S, Zhang Yucai Y, Ma Chenghong C, Wen Huixin H et al.
Somatic wasting and psychological distress frequently cluster in patients on maintenance hemodialysis (MHD), but their longitudinal joint trajectories and germline-level causal pathways with downstream dopamine metabolism in restless legs syndrome (RLS) remain unclear. This multi-stage study combined a prospective cohort and genetic triangulation. First, within a matched 5-year longitudinal MHD cohort (N = 192), multivariable generalized estimating equations (GEE) and latent growth curve mediation models (LGCM) quantified time-dynamic risks and decomposed trajectory mediation pathways. Findings were validated via landmark diagnostics and replicated in the full unmatched imputed cohort (N = 321). Second, bidirectional and network two-sample Mendelian randomization (MR) utilized independent GWAS statistics to map genetically predicted renal impairment (eGFR/UACR) against plasma dopamine 3-O-sulfate levels via psychological and musculoskeletal traits. Longitudinal GEE revealed that sarcopenia (Adjusted OR = 1.58, p = 0.002) and depressive severity (Adjusted OR = 1.10, p < 0.001) independently predicted 5-year incident RLS, compounded by a significant multiplicative interaction (OR = 1.50, p < 0.012). Decoupled LGCMs showed that chronic trajectories of depression, anxiety, frailty, and sarcopenia mediated 44.4, 45.5, 45.8, and 46.2% of the total risk pathways, respectively (all p < 0.001). MR triangulation confirmed that lower eGFR causally associated with increased depression risk (IVW: IVW: β = -0.579, p = 0.004), which directionally mediated a substantial indirect effect on suppressed dopamine 3-O-sulfate metabolism (indirect effect: 0.401, p = 0.004; accounting for 41% of the total effect), whereas anxiety lacked mediating reliability. This study establishes a stable somatopsychic-neurological cascade where chronic phenotypic deterioration and genetically predicted depression mediate the pathway from renal impairment to suppressed dopamine metabolism, highlighting multi-system targets for early RLS screening and preventive intervention.
Matsumoto Kenjiro K, Nakamoto Tomohiro T, Sato Akari A, Utsumi Daichi D et al.
Transient receptor potential melastatin 8 (TRPM8) is a cold-sensitive Ca2+-permeable ion channel that regulates intestinal inflammation. This study was aimed to elucidate the role of TRPM8 in enteric macrophages and spinal afferent sensory neurons during dextran sulfate sodium (DSS)-induced colitis. The role of TRPM8 in the progression of colonic inflammation was examined in 2% DSS-induced colitis by immunohistochemistry, reverse transcription-polymerase chain reaction, visceral sensing assessment, and flow cytometry. The role of TRPM8 in sensory neurons and macrophages was investigated using primary cultured dorsal root ganglion (DRG) neurons and bone marrow-derived macrophages (BMDMs). DSS-induced colitis was significantly aggravated in TRPM8-deficient (KO) mice compared with that in wild-type (WT) mice. In the colitis model, KO mice showed lower IL-10 mRNA levels than WT mice, but IL-6, IL-1β, and TNF-α levels were not affected. TRPM8 expression was upregulated in the distal colon and DRG following DSS administration. In the distal colon, TRPM8-immunoreactive cells and nerve fibers colocalized with F4/80 and substance P/calcitonin gene-related peptide (CGRP), respectively. In the DRG, TRPM8 neuron subtypes were labeled by neurofilament 200, substance P, CGRP, and tyrosine kinase receptor A. In cultured DRG neurons, TRPM8 deficiency attenuated lipopolysaccharide (LPS)-elicited CGRP release but did not affect substance P release. In BMDMs, TRPM8 deficiency significantly decreased LPS- and LPS/CGRP-elicited upregulation of IL-10 mRNA compared with that in WT animals. TRPM8 protects against DSS-induced experimental colitis via regulating CGRP release from sensory neurons and IL-10 production in enteric macrophages during intestinal inflammation.
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