Miostat (carbachol) / Alcon - LARVOL DELTA

Enhanced mucosal contractile activity following rapid, reversible inhibition of bladder activity by dimethyl sulfoxide (DMSO). (PubMed, World J Urol) - "These results demonstrate the powerful, but reversible, effects of DMSO on detrusor and mucosal contractile activity. The enhanced mucosal contractile activity upon washout may explain the flare up of symptoms observed in some patients following treatment."

Journal • Interstitial Cystitis • Musculoskeletal Pain • Pain

Sustained FLAP inhibition with fiboflapon dampens airway smooth muscle reactivity in guinea pig trachea (ERS 2026) - "Isometric contractions were recorded using a myograph and responses to KCl, histamine, carbachol and the thromboxane A2 mimetic U-46619 were assessed. Acute exposure to fiboflapon did not alter responses to KCl or histamine, whereas 48 h treatment reduced ASM sensitivity to histaminergic, cholinergic and thromboxane- agonists as well as to depolarization. These findings suggest that sustained FLAP inhibition could provide clinically relevant protection against bronchoconstriction by broadly reducing airway hyperresponsiveness to multiple bronchoconstrictor pathways in asthma."

Asthma • Immunology • Respiratory Diseases

Non-Neuronal Cholinergic Signaling Drives Aggressive Small Cell Lung Cancer via Targetable Choline Transport (IASLC-WCLC 2026) - "Cholinergic stimulation (nicotine, ACh, neostigmine, carbachol) significantly enhanced proliferation, supporting an autocrine cholinergic growth loop...Their co-upregulation reflects transporter co-dependency and identifies a targetable metabolic vulnerability. Pharmacologic inhibition of choline transport using Amb4269951 and Amb4269675 provides a novel therapeutic strategy for refractory SCLC."

Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • ASCL1 • CASP3 • CASP7 • INSM1 • MKI67

Synergistic effects of agonists on CFTR in intestinal epithelia (NACFC 2026) - " Human intestinal epithelial T84 cells were used to assess the effects of the purinergic agonist ATP and the cholinergic agonist carbachol (CCh) on Cl− secretion and CFTR activity... ATP pretreatment enhances CFTR activation in response to subsequent cholinergic stimulation in a temporally dependent manner. This potentiation is mediated through adenosine signaling and involves PKA and calmodulin pathways. These findings identify a synergistic regulatory mechanism that could be leveraged to augment CFTR function in the gut to improve GI outcomes in CF."

CD73

Endogenous tracking reveals paralog-specific targets for phosphatidic acid generation during phospholipase C signaling in living cells. (PubMed, J Biol Chem) - "Live-cell imaging experiments using BMS-502 with carbachol stimulation of endogenous muscarinic receptors showed that inhibition of both DGKα and the PLDs is needed to substantially reduce PA levels during PLC activation. Our findings both identify paralog-specific druggable targets for modulating PLC signaling events, and establish a new platform for characterizing DGK and PLD activity in living cells."

Journal

High-fat diet feeding reduced smooth muscle contractility and increasing tissue programmed death activity in rats bladder tissue. (PubMed, Int Urol Nephrol) - "Chronic HFD feeding induces bladder dysfunction through smooth muscle impairment, fibrotic remodeling, and activation of multiple programmed cell death pathways, with compensatory enhancement of purinergic signaling via P2X₂ receptors. These findings provide mechanistic insight into metabolic syndrome-related bladder disorders and identify potential therapeutic targets."

Journal • Preclinical • Atherosclerosis • Dyslipidemia • Fibrosis • Immunology • Metabolic Disorders • Urology

Development of covalent agonists for the muscarinic acetylcholine receptor. (PubMed, Bioorg Med Chem) - "Using the muscarinic acetylcholine receptor (mAChR) agonists iperoxo (5), PR15 (7), and carbachol (9) as lead compounds, we developed the covalent muscarinic receptor agonists 8 and 10 functionalized by a mustard-type reactive group. Radioligand depletion and functional properties clearly indicated covalent binding and activation of the therapeutically relevant muscarinic acetylcholine receptor."

Journal

Aquaporin-1 facilitates the transport of hydrogen peroxide and nitric oxide during endothelium-dependent vasorelaxation. (PubMed, Vascul Pharmacol) - "Incubation with diphenyleneiodonium (non-specific NADPH oxidase inhibitor), VAS2870 (pan-NADPH oxidase inhibitor), diethyldithiocarbamate (superoxide dismutase inhibitor), exogenous peroxidase, AgNO3 (non-selective AQP inhibitor), or bacopaside II (selective AQP1 inhibitor) significantly attenuated carbachol-stimulated endothelium-dependent relaxation...Furthermore, both AgNO3 and bacopaside II decreased relaxation mediated by the intracellular NO donor sodium nitroprusside...Collectively, these findings suggest that during endothelium-dependent vasorelaxation, AQP1 facilitates endothelial H2O2 influx and subsequent NO efflux, rather than promoting their entry into vascular smooth muscle cells. Thus, our work uncovers a coordinated H2O2-NO signaling cascade that drives endothelium-dependent relaxation in the rat aorta via AQP1-mediated transport, providing novel insights into the biophysical mechanisms governing endothelial function."

Journal • AQP1

Effects of Vonoprazan on Isolated Rat Lower Esophageal Sphincter and Ileum. (PubMed, Pharmaceuticals (Basel)) - "The direct relaxant effects of cumulative vonoprazan were assessed in tissues precontracted with carbachol. These results indicate that vonoprazan directly inhibits gastrointestinal smooth muscle contractile activity by decreasing spontaneous ileal contraction amplitudes and attenuating muscarinic and serotonergic contractile responses in isolated rat ileum and LES. Further studies are required to determine the underlying mechanisms and clinical relevance of these effects."

Journal • Preclinical • Gastroenterology • Gastroesophageal Reflux Disease

Prostaglandin E2 modulates contractility of mouse bladder smooth muscle cells. (PubMed, Front Physiol) - "The effects of PGE2 alone and in combination with increasing concentrations of carbachol (CCh) were assessed by measuring oscillation active time, frequency, and duration of Ca²+ events...PGE2 acts as a local excitatory modulator of mouse detrusor smooth muscle, increasing spontaneous Ca2+ activity and sensitizing the tissue to cholinergic stimulation. These effects are associated primarily with frequency-based modulation of Ca2+ oscillations and may represent a cellular mechanism contributing to detrusor overactivity under conditions of increased prostaglandin signaling."

Journal • Preclinical • Overactive Bladder

Calcium channel blocking activity as a mechanism of the spasmolytic effect of menthol on isolated bovine ileum. (PubMed, Vet Res Forum) - "The tissues were subjected to various contractile agents, including potassium chloride at concentrations of 30.00 and 80.00 mM, carbachol chloride at 1.00 and 4.00 μM and barium chloride at 30.00 mM. Menthol was cumulatively applied in incremental concentrations to assess its modulatory effects on contraction amplitude...The Ca2+ channel blocking activity was further confirmed when pre-treatment of isolated ileums with menthol (23.00 and 200 μg mL-1) caused a rightward shift in the Ca2+ concentration-response curves, similar to verapamil. These findings suggested that menthol spasmolytic action might be mediated through the modulation and inhibition of calcium channels. In conclusion, menthol effectively attenuated bovine ileal smooth muscle contractions in vitro, indicating its potential as a natural therapeutic agent for controlling gastrointestinal hyperactivity in cattle."

Journal

High-throughput UHPLC-MS/MS analysis of Cystatin C proteoforms and creatinine in human sweat for kidney function monitoring. (PubMed, Anal Chim Acta) - "The workflow integrates iontophoresis-based sweat induction using pilocarpine or carbachol as stimulating agent, sweat collection on bovine serum albumin-pretreated filter paper to minimize analyte adsorption, micro-extraction by packed sorbent sample clean-up and analyte preconcentration, and proteoform-resolved analysis by liquid chromatography-tandem mass spectrometry. Overall, this study provides proof-of-concept evidence supporting the feasibility of proteoform-resolved LC-MS/MS analysis of sweat for kidney function assessment. The molecular specificity afforded by this approach, beyond that of conventional immunoassays, highlights its potential for biomarkers characterization and warrants further investigation toward patient-centered and longitudinal CKD assessment strategies."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease • CST3

Molecular regulatory mechanism of TRPV4-mediated calcium-dependent 5-HT secretion from enterochromaffin cells and its involvement in ulcerative colitis. (PubMed, PLoS One) - "Carbachol (CCh), a stable analog of ACh, activated mAChR/IP3/IP3R pathway to increase intracellular [Ca2+]ilevels in ECs, in which both TRPV4 channels and RyR were activated in response to CCh...In addition, selective blocker of RyR (Dantrolene) also significantly inhibited CCh-induced calcium signals and membrane currents...Taken together, this study reveals a novel mAChR/IP3/IP3R /TRPV4/5-HT pathway in ECs is likely involved in the pathogenesis of UC. Targeting this pathway holds a promise for the potential prevention and treatment of UC."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Neocortical pyramidal cells with axon-carrying basal dendrites: a prominent feature regulated by activity. (PubMed, Brain Struct Funct) - "In contrast, perinatal enhancement of glutamatergic network activity with kainate or carbachol via subplate neurons accelerated the appearance of AcD pyramidal neurons. None of the treatments altered the proportion of AcD interneurons. Together, the larvae stage of a cortical AcD pyramidal neuron can well be the DcA configuration, and the formation of basal AcDs was - at least transiently - regulated by neuronal activity, calcium and glutamatergic signaling."

Journal • GRIN2B

Phosphatase Inhibition Attenuates the Negative Inotropic Effect of Muscarinic Receptors in the Presence of Serotonin. (PubMed, Curr Issues Mol Biol) - "These anti-β-adrenergic, anti-serotoninergic and anti-histaminergic effects of carbachol on force of contraction were attenuated by 100 µM or 30 µM cantharidin or 3 mM sodium fluoride in HAP and in left atrial preparations from WT, H2-TG, and 5-HT4-TG, respectively. We conclude that muscarinic cholinoceptor activation may exert a negative inotropic effect in the HAP by stimulating PP1 and/or PP2A, which had previously been inhibited by isoprenaline or histamine or serotonin."

Journal

Phenolic and Terpenic Composition of Salvia guaranitica (Lamiaceae) Hydroethanolic Extract and Cardioprotective, Intestinal, and Anxiolytic Effects. (PubMed, Plants (Basel)) - "Antispasmodic effects of S.g-T were evaluated on contractile concentration-response curves (CRCs) of carbachol (CCh) and calcium (Ca2+) in rat isolated intestinal tissue...In vivo, S.g.-T showed antidiarrheal activity (95 mg extract/kg) and anxiolytic-like effects (0.95-9.5 mg extract/kg) without sedation or antidepressant-like effects. Therefore, S. guaranitica leaves have potential therapeutic cardioprotective, antidiarrheal, antispasmodic and anxiolytic effects."

Journal • Anesthesia • Cardiovascular • Reperfusion Injury

Bronchorelaxant and anti-inflammatory profile of ensifentrine alone and combined with inhaled medications in lipopolysaccharide-challenged human airways from chronic obstructive pulmonary disease donors. (PubMed, J Pharmacol Exp Ther) - "The effects of ensifentrine on bronchial relaxation were evaluated in response to carbachol and electrical field stimulation (EFS), also in combination with long-acting muscarinic antagonist (LAMA), long-acting β2-adrenoceptor agonists (LABA), and inhaled corticosteroids (ICS). It exhibits synergistic interactions with existing inhaler therapies, enhancing their efficacy. By demonstrating anti-inflammatory efficacy comparable to the established PDE4 inhibitor, roflumilast, our findings emphasize ensifentrine's capacity to significantly improve treatment outcomes and guide the development of optimized future combination strategies for COPD management."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Oncology • Pulmonary Disease • Respiratory Diseases • IL10 • TNFA

On indirect negative inotropic effects of muscarine in the isolated human atrium. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "After application of 1 µM isoprenaline (to stimulate β-adrenoceptors) or 1 µM serotonin (to stimulate 5-HT4-serotonin receptors) or 1 µM histamine (to stimulate H2-histamine receptors) or 10 µM fenoldopam (to stimulate D1-dopamine receptors) or 100 nM semaglutide (to stimulate glucagon-like-peptide-1 receptors) or 100 nM gastric inhibitory peptide (to stimulate the gastric inhibitory peptide receptors) additionally applied 1 µM muscarine reduced FOC...We conclude that muscarine in the presence of several cAMP-increasing agents or a cAMP-dependent protein kinase activating agent exerts negative inotropic effects in HAP. These contractile responses might underlie negative inotropic effects in muscarine intoxications in the clinic."

Journal • Cardiovascular • Coronary Artery Disease • Heart Failure

Ethnopharmacological Validation of Capparis spinosa L. in Gastrointestinal and Respiratory Disorders: Evidence from In Vitro, In Vivo, and In Silico Models. (PubMed, J Ethnopharmacol) - "C. spinosa L. exerts potent antispasmodic, bronchodilator, and antidiarrheal effects and may involve Ca2+ channel blockade and muscarinic antagonism, demonstrating pharmacological justification for its traditional use in gut and airway dysfunctions."

Journal • Preclinical • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Secoisolariciresinol diglucoside ameliorates muscarinic acetylcholine receptor mediated activation of NLRP3 inflammasome in cardiomyocytes. (PubMed, Mol Biol Rep) - "The study revealed the beneficial therapeutic properties of SDG as an anti-inflammatory agent that can help prevent NLRP3-induced inflammation. Further, the findings highlight the pro-inflammatory property of muscarinic cholinergic system, in contrast to the known nicotinic cholinergic anti-inflammatory system."

Journal • Cardiovascular • Inflammation • IL18 • IL1B • NLRP3

Cryptotanshinone as a Multi-Target Natural Terpenoid with Bronchodilator Potential: Insights from Integrated In Vitro and In Silico Studies. (PubMed, Molecules) - "The relaxant effects of CT (10-7-3 × 10-4 M) were evaluated against carbachol (1 µM)- and high-K+ (80 mM)-induced contractions...Pharmacological inhibition studies indicated the involvement of muscarinic receptor-mediated mechanisms, with additional contributions from calcium channel-related mechanisms and partial involvement of the NO/cGMP pathway, while β2-adrenergic signaling and potassium channels were not significantly involved. These findings suggest that CT exerts bronchodilatory effects through the involvement of multiple pharmacological pathways relevant to airway smooth muscle regulation and provide preliminary mechanistic evidence supporting further investigation."

Journal • Preclinical • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Discovery and optimization of diarylsulfone-based dual M3-Antagonists and β2-Agonists (MABAs) as inhaled bronchodilators. (PubMed, Eur J Med Chem) - "We report the discovery and optimization of MABAs by integrating a diarylsulfone scaffold with the hydroxyquinoline moiety of indacaterol 2 to achieve dual M3 and β2 activity...Lead compounds 150 and 160 showed high-affinity and long-lived binding to M3 (Ki: 1.95 nM and 1.75 nM, respectively, at 24 h) and subnanomolar β2-agonist potency, along with excellent (EC50 < 10 nM) smooth muscle relaxant activity in carbachol-stimulated guinea pig trachea rings. Moreover, after intratracheal administration, both compounds exhibited sustained in vivo bronchoprotection for 24 h in the modified Einthoven model of acute bronchoconstriction, with equivalent efficacy to the clinical-stage MABA batefenterol 9. Further development of these compounds is warranted as inhaled bronchodilators."

Journal • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Loss of TRPV4 impairs mucin secretion and salivary rheological properties in male mouse sublingual glands. (PubMed, Odontology) - "This study used an ex vivo perfusion model to investigate the contribution of TRPV4 to mucin secretion and the rheological properties of saliva in wild-type (Trpv4⁺/⁺) and knockout (Trpv4⁻/⁻) male mice (8-12 weeks old) subjected to carbachol stimulation...Muc19 mRNA expression and intracellular MUC19 distribution were unaffected, whereas MUC19 protein in secreted saliva was significantly lower in Trpv4⁻/⁻ mice. These findings indicate that TRPV4 contributes to mucin secretion in SLG acinar cells independently of fluid secretion and Muc19 transcriptional regulation, likely at the level of exocytosis."

Journal • Preclinical • MUC19 • OVGP1

Calcium-Driven Gs-to-Gq Switching of GLP-1 Receptor Signaling in Pancreatic Β-Cells under High-Glucose Conditions (ENDO 2026) - "Notably, similar glucose-dependent modulation–suppression of cAMP and augmentation of IP1–was observed following stimulation with multiple ligands, including GIP and glucagon (Gs-dependent) as well as carbachol and LPI (Gq-dependent)...Importantly, this glucose-induced signaling modulation was reversed by treatment with the calcium-channel blocker nifedipine or the potassium-channel opener diazoxide, both of which reduce calcium influx...While GPCRs are generally capable of coupling to multiple G proteins, the relative strength of downstream signaling is finely tuned by cellular context. To our knowledge, this study provides the first evidence of calcium-driven, effector-level biased modulation of GPCR signaling, mediated through differential regulation of AC and PLC."

Diabetes

Ethnopharmacological basis for folkloric claims of Tradescantia spathacea to treat Gastrointestinal Spasm and Respiratory Distress via In-vitro, In-vivo and In-silico approaches. (PubMed, J Ethnopharmacol) - "The findings provide pharmacological evidence supporting the traditional use of TS. Cr. in respiratory and gastrointestinal disorders. The observed bronchodilator, spasmolytic, and antidiarrheal effects may be mediated through potassium channel activation and antimuscarinic mechanisms."

Journal • Preclinical • Asthma • Cough • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases