pyridostigmine Bromide / Generic mfg. - LARVOL DELTA

Pharmacodynamics, Safety, and Tolerability of Pyridostigmine Bromide in Heart Failure. (PubMed, Curr Ther Res Clin Exp) - P2 | "Further investigations are needed to delineate pharmacodynamic and pathobiological factors contributing to these findings. ClinicalTrials.gov identifier: NCT01415921."

Clinical • Journal • PK/PD data • Cardiovascular • Congestive Heart Failure • Heart Failure

Age- and sex-associated effects of C18 ceramide sphingolipids on osteoclastogenesis in experimental models of Gulf War Illness. (PubMed, Biomed Pharmacother) - "Approximately 60 % of Gulf War Illness (GWI) cases are correlated with toxic exposure to permethrin (PER) and pyridostigmine bromide (PB) in Veterans...In addition, C18:1 diminished RANKL-primed osteoclastogenesis in young male as well as young and aged female mouse osteoclast precursors in the presence of PER in vitro. As Veterans with GWI rapidly approach the senior 65+ age range, further studies are warranted to evaluate the potential link between Gulf War toxic exposure and ceramide sphingolipids in age- and sex-associated osteoclastogenesis."

Journal

Modeling gulf war illness: Anxiety, memory deficits, cholinergic and Potassium Channel imbalance in male and female mice. (PubMed, Life Sci) - "We modeled a GW-like exposure in male and female C57BL/6 J mice using pyridostigmine bromide (PB), permethrin (PER), N, N-diethyl-meta-toluamide (DEET), moderate stress, and Diisopropylfluorophosphate (DFP), a sarin analog...Proteomics analysis supported the presence of sex-dependent neurobiological alterations, with both sexes showing disruptions in proteins involved in neuronal signaling and mitochondrial metabolism, yet involving distinct molecular signatures. These findings underscore the sexually dimorphic nature of GWI pathophysiology."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Mood Disorders • Pain • Psychiatry • CHAT • GFAP

Vagal Stimulation in POTS (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: Vanderbilt University Medical Center | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Cardiovascular

Atherosclerotic Cardiovascular Disease in Gulf War Veterans in Relation to Deployment Exposures. (PubMed, Cardiovasc Toxicol) - "Many 1990-1991 Gulf War Veterans (GWVs) were exposed to toxicants and environmental hazards during deployment, including oil well fire smoke, chemical/biological agents, pyridostigmine bromide (PB) pills, and pesticides...For GWVs, exposure to oil well fire smoke, chemical/biological agents, and PB pills were associated with ASCVD. These exposures may represent population-specific risk enhancers for ASCVD and may be considered in individualized clinical risk assessment."

Journal • Atherosclerosis • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders

Comprehensive examination of resting state fMRI connectomics yields new insights into brain function deficits in Gulf War illness after accounting for heterogeneity in brain impairment across the ill veteran population. (PubMed, Neuroimage Rep) - "Epidemiologic and animal studies have associated GWI with exposure to neurotoxic chemicals such as nerve agents, organophosphate pesticides and pyridostigmine bromide...The findings indicate that these deficits may by and large be driven by brain mechanisms. We also found that pooling the data of all three syndromes in GWI group, as is done by commonly employed case definitions of GWI resulted in failure to detect the fMRI signatures of a lot of these brain impairments."

Heterogeneity • Journal

Mitochondria-targeted therapy with metformin and MitoQ reduces oxidative stress, improves mitochondrial function, and restores metabolic homeostasis in a murine model of Gulf War Illness. (PubMed, Redox Biol) - "A GWI model in C57BL/6 mice exposed to the nerve gas prophylactic pyridostigmine-bromide (PB) and the insecticide permethrin (PER) was used to test the effect of mitochondria-potentiating agents, metformin and MitoQ on chronic fatigue, observed in GWI. Chronic fatigue assessments by the hanging wire and rotarod tests, and voluntary wheel running activities showed improved physical activity/strength in mice treated with metformin and MitoQ. The results suggest the potential therapeutic benefit of a combination formulation of metformin and MitoQ in addressing the molecular and energetic impairments of skeletal muscle in GWI."

Journal • Preclinical • Fatigue • Inflammation

In vitro evaluation of isatin-pyridine oxime hybrids as potential acetylcholinesterase inhibitors for nerve agent prophylaxis. (PubMed, Chem Biol Interact) - "Compounds 14 and 15 evidenced inhibitiory ability (226.4 and 24.7 μM of IC50, respectively), and this last was similar to compound reference pyridostigmine bromide, the only reported drug used as prophylactic measure for nerve agent exposure. Results suggest promisor dual-functional compounds for nerve agent prophylaxis and the reactivation of enzyme catalytic activity."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Pain

Resveratrol ameliorates cognitive impairment with improvement of gut microbiota, inflammation, neurogenesis, and synaptic proteins in a mouse model of Gulf War Illness. (PubMed, Eur J Pharmacol) - "Five months after exposure to 0.7 mg/kg pyridostigmine bromide (PB) and 200 mg/kg permethrin (PER), a two-week regimen of RSV at doses of 20 or 40 mg/kg alleviated the cognitive deficits observed in the object location and novel object recognition tests. RSV treatment effectively mitigates cognitive disorders through multiple mechanisms: (1) amelioration of gut microbiota dysbiosis and intestinal permeability; (2) downregulation of serum proinflammatory cytokine levels; (3) suppression of chronic neuroinflammation in the hippocampus, evidenced by reduced astrocyte hypertrophy, microglial activation, and neuroinflammatory markers; (4) promotion of hippocampal neurogenesis; and (5) normalization of synaptic protein levels, including PSD95, CaMKIIα. This study provides novel insights into the potential of RSV to alleviate cognitive impairment, alongside the restoration of gut dysbiosis, in veterans suffering from GWI."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Inflammation • DLG4

Persistent enteric neuroinflammation chronically impairs colonic motility in a pyridostigmine bromide-induced mouse model of Gulf War Illness. (PubMed, Biol Open) - "Together, our findings suggest that persistent enteric neuroinflammation and impaired neurogenesis contribute to long-term colonic dysmotility in GWI. This model offers new insights into chronic ENS dysfunction and may guide therapeutic strategies for GWI and related disorders."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Inflammation

α7nAChR on B cells directs T cell differentiation to prevent viral myocarditis. (PubMed, JCI Insight) - "The acetylcholinesterase inhibitor pyridostigmine bromide could improve cardiac remodeling and prevent the progression of VMC to the chronic phase, which was partly dependent on the α7nAChR on B cells. Our findings provide notable insights into cardiac-neural-immune communication during myocardial injury."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Inflammation • IL17A

A Case Report of NMOSD Hidden Beneath MG and Cervical Spondylosis with Imaging Changes of Cervical Cord Compression: The Dual Therapeutic Effect of Inebilizumab (AAN 2025) - "The patient was diagnosed with AQP4 antibody-positive NMOSD complicated by MG and cervical spondylosis, with EDSS score of 2 and ADL score of 5.The patient received corticosteroid pulse therapy and pyridostigmine bromide, followed by inebilizumab. Clinicians should be vigilant in differentiating cervical spondylosis with cervical cord compression from NMOSD to avoid misdiagnosis and unnecessary surgery. NMOSD typically presents as long-segment that are centrally located, whereas cervical spondylosis with cervical cord compression often involves short segments, progressing from the compression site toward the center, with lesion size proportional to the degree of compression. AQP4 antibody-positive NMOSD and AChR antibody-positive MG are both IgG-mediated diseases that respond well to B-cell depletion therapy."

Case report • Clinical • CNS Disorders • Myasthenia Gravis • Neuromyelitis Optica Spectrum Disorder • Rare Diseases

Myasthenia gravis complicated by pure red cell aplasia with clonal large granular lymphocytosis in the absence of thymoma: a rare case report and literature review. (PubMed, Front Immunol) - "Her muscle weakness was subsequently well-controlled with pyridostigmine bromide, azathioprine, and prednisone. This unique case highlights the unprecedented association of MG and PRCA without thymoma, underscoring the complexity of the disease spectrum. The patient's subsequent successful delivery in June 2023 adds another dimension to the multifaceted clinical course, warranting attention and exploration into potential connections between these conditions."

Journal • Review • CNS Disorders • Hematological Disorders • Immunology • Infectious Disease • Myasthenia Gravis • Respiratory Diseases • Solid Tumor • Thymoma • Thymus Cancer

Additive Value of Pyridostigmine to Silodosin in the Management of Acute Urinary Retention Secondary to Benign Prostatic Hyperplasia: A Randomized Controlled Trial. (PubMed, J Clin Med) - P2 | " The combination of pyridostigmine bromide (60 mg tablet) with silodosin proved to be more effective than silodosin alone in managing acute urinary retention caused by BPH. This was particularly true for patients who were suspected to have detrusor underactivity in addition to BPH."

Journal • Benign Prostatic Hyperplasia • Pain • Urology

Clinical Correlates of Efficacy of Pyridostigmine in the Treatment of Orthostatic Hypotension. (PubMed, Hypertension) - P1 | "Importantly, in this cohort of patients with severe autonomic failure, pyridostigmine was not effective in those with supine hypertension who would benefit the most from the preferential pressor effect of the drug on upright BP. URL: http://www.clinicaltrials.gov; Unique identifier: NCT00223691."

Journal • Cardiovascular • CNS Disorders • Hypertension • Hypotension • Movement Disorders • Multiple System Atrophy

Impact of SARS-CoV-2 infection on patients with myasthenia gravis: a retrospective study in a Chinese population. (PubMed, Front Neurol) - "Multivariate analysis indicated that thymectomy [OR, 1.654 (95% CI, 1.036-2.643); p = 0.035], severe SARS-CoV-2 infection [OR, 4.275 (95% CI, 2.206-8.286); p < 0.001], and pyridostigmine bromide [OR, 1.955 (95% CI, 1.192-3.206); p = 0.008] were associated with exacerbation of MG symptoms in patients infected with SARS-CoV-2...Due to the retrospective nature of the study, these findings should be interpreted as associations rather than predictive factors. However, the results confirm the established relationships between severe SARS-CoV-2 infection and age, cardiovascular comorbidities, and the use of steroid treatment, suggesting that these factors should be considered when managing MG patients during SARS-CoV-2 infection."

Journal • Retrospective data • Cardiovascular • CNS Disorders • Infectious Disease • Myasthenia Gravis • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Telitacicept and Low-dose Steroids in Refractory Myasthenia Gravis (clinicaltrials.gov) - P4 | N=30 | Not yet recruiting | Sponsor: First Affiliated Hospital of Wenzhou Medical University

New P4 trial • CNS Disorders • Immunology • Myasthenia Gravis

Myasthenia gravis after allogeneic hematopoietic stem cell transplantation: Two case reports and literature review (PubMed, Zhonghua Xue Ye Xue Za Zhi) - "The acetylcholine receptor (AChR) antibody and neostigmine test enabled the diagnosis of MG. The condition of the patients improved after treatment with pyridostigmine bromide, glucocorticoids and rituximab."

Journal • Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • CNS Disorders • Hematological Malignancies • Leukemia • Myasthenia Gravis • Oncology • Pulmonary Disease • Transplantation

Contributions of the gut microbiota to Gulf War Illness susceptibility: Findings from a mouse model. (PubMed, Life Sci) - "To our knowledge, this is the first preclinical report in which a stratification by susceptibility to GWI and its association with the gut microbiome is described. In light of the research conundrum that vulnerability to GWI represents, the use of tools that could provide further insight into this complex factor should be considered."

Journal • Preclinical • Gastrointestinal Disorder • Pain

PESTI: Pyridostigmine Efficacy and Safety for Treatment of Ileus After Colorectal Surgery (clinicaltrials.gov) - P2/3 | N=50 | Recruiting | Sponsor: Stefan Holubar MD MS FACS, FASCRS | Not yet recruiting ➔ Recruiting | Trial completion date: Jan 2026 ➔ Oct 2025 | Trial primary completion date: Dec 2025 ➔ Sep 2025

Enrollment open • Surgery • Trial completion date • Trial primary completion date

Association of deployment characteristics and exposures with persistent ill health among 1990-1991 Gulf War veterans in the VA Million Veteran Program. (PubMed, Environ Health) - "Results from this large cohort indicate that GWI/chronic ill health continues to affect a large proportion of Gulf War veterans in patterns associated with 1990-1991 Gulf War deployment and exposures. Findings establish a foundation for comprehensive evaluation of genetic factors and deployment exposures in relation to GWI risk and pathobiology."

Journal • MVP

Laryngeal Myasthenia Gravis in Voice Patients: Clinical, Serologic, and Neuromuscular Characterization of Seronegative Patients for Antibodies Against the Acetylcholine Receptor and Muscle-Specific Kinase. (PubMed, J Voice) - "Laryngeal MG is an underrecognized condition in the otolaryngology community owing in part to its seronegative presentation. Electrical improvement with a Tensilon test, or electrical or substantial symptomatic improvement with pyridostigmine bromide represents the most robust diagnostic criteria in these patients."

Journal • CNS Disorders • Dysphonia • Myasthenia Gravis • Otorhinolaryngology

The Effects of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive Individuals With Spinal Cord Injury (clinicaltrials.gov) - P2 | N=21 | Completed | Sponsor: James J. Peters Veterans Affairs Medical Center | N=41 ➔ 21

Enrollment change • CNS Disorders • Hypotension • Orthopedics

Military and occupational exposures among Veterans in the Million Veteran Program by survey self-report: a descriptive study. (PubMed, Occup Environ Med) - "Our results demonstrate that the distribution of self-reported exposures varied by service era, demographics, deployment, combat experience and military occupation in MVP. Overall, the pattern of findings was consistent with previous population-based studies of US military Veterans."

Journal

Longitudinal evaluation of structural brain alterations in two established mouse models of Gulf War Illness. (PubMed, Front Neurosci) - "In the PB/PM model, male C57BL/6 J mice (8-9 weeks) received daily exposure to the nerve agent prophylactic pyridostigmine bromide (PB) and the pyrethroid insecticide permethrin (PM) for 10 days...Behaviorally, at 13 months, motor function was largely preserved in both models. However, the GWI mice in the PB/DEET/CORT/DFP model exhibited an elevation in anxiety-like behavior."

Journal • Preclinical • Mood Disorders • Psychiatry