imidafenacin / Generic mfg. - LARVOL DELTA

Evaluation of the Potential Inhibitory Effects of Medications for Detrusor Overactivity on Platelet-Activating Factor (PAF)-Induced Mechanical Activity in Guinea Pig Bladder Smooth Muscle. (PubMed, Biol Pharm Bull) - "Ten clinically used DO drugs-oxybutynin, tolterodine, fesoterodine, propiverine, propantheline, solifenacin, imidafenacin, flavoxate, urapidil, and clenbuterol-were tested at a concentration of 10 μM, exceeding typical therapeutic plasma levels. Furthermore, oxybutynin (10 μM) also decreased 60 mM KCl-induced contractions by a similar extent and nearly abolished acetylcholine (ACh, 10 μM)-induced contractions. These findings suggest that oxybutynin suppresses PAF-induced UBSM hyperactivity through a mechanism distinct from its anticholinergic effect, likely mediated by blockade of voltage-dependent Ca2+ channels (VDCCs)."

Journal • Overactive Bladder

Additive effects of mirabegron on muscarinic receptor binding and on relaxation of cholinergic detrusor muscle contraction by antimuscarinics. (PubMed, J Pharmacol Sci) - "Muscarinic receptor binding activity and inhibitory effect on carbachol-induced contraction in rat tissues were evaluated by radioreceptor assays using [N-methyl-3H]scopolamine chloride (3HNMS) and the organ-bath procedure, respectively...Moreover, the inhibitory effects of solifenacin and imidafenacin on carbachol-induced contractions in rat isolated bladder strips were increased by mirabegron, particularly at lower concentrations of solifenacin and imidafenacin. This is the first study to suggest that mirabegron in combination with antimuscarinics exerts additive effects for muscarinic receptor binding and inhibitory effects on cholinergic contractions in bladder strips. The results obtained also showed that these additive effects may contribute to enhanced therapeutic effects on OAB, but also cholinergic adverse effects."

Journal • Overactive Bladder • Xerostomia

Development of long-acting imidafenacin transdermal patches with high drug loading based on solid dispersion technology. (PubMed, Int J Pharm) - "Notably, under long-term and accelerated conditions of 3 months, the LAITP exhibited excellent stability to ensure the reliability of quality. Importantly, human pharmacokinetic studies demonstrated that LAITP with low skin irritation and favorable adhesion properties prolonged sustained effective plasma concentration in comparison to commercial tablets (Staybla®), reducing the frequency of administration and thereby improving patient compliance, which is expected to be a promising treatment option for patients with OAB."

Journal • Overactive Bladder

Mirabegron Versus Placebo and Other Therapeutic Modalities in the Treatment of Patients with Overactive Bladder Syndrome-A Systematic Review. (PubMed, Eur Urol Focus) - "Mirabegron is effective, safe, and well tolerated. Coadministration with anticholinergics provides an advantageous additive effect without a higher occurrence of side effects."

Journal • Review • Overactive Bladder • Urinary Incontinence • Urology

Efficacy and safety evaluation of imidafenacin administered twice daily for continency recovery following radical prostatectomy in prostate cancer patients: Prospective open-label case-controlled randomized trial. (PubMed, Investig Clin Urol) - "In the case of urinary incontinence that occurs after RARP, even if the function of the intrinsic sphincter is sufficiently preserved, if urinary incontinence persists due to changes in the bladder, pharmacological therapy using imidafenacin can be beneficial in managing urinary incontinence."

Clinical • Journal • Genito-urinary Cancer • Oncology • Overactive Bladder • Prostate Cancer • Solid Tumor • Urinary Incontinence • Urology

Efficacy and safety evaluation of imidafenacin administered twice daily for continency recovery following radical prostatectomy in prostate cancer patients (UAA 2024) - No abstract available

Clinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Effectiveness of Mirabegron VS. Imidafenacin in Improving Double J stent-related Symptoms: An Initial Prospective Open Interventional Study. (UAA 2024) - No abstract available

Clinical

Predicting muscarinic receptor occupancy in human bladder mucosa from urinary concentrations of antimuscarinic agents for overactive bladder. (PubMed, Drug Metab Pharmacokinet) - "The bladder muscarinic receptor occupancy was higher than that in the parotid gland calculated based on the mean plasma or serum unbound concentrations and Ki values for muscarinic receptors in the parotid gland. These results suggest that sufficient and selective muscarinic receptor occupancy by antimuscarinic agents, to exert pharmacological effects, in the bladder mucosa can be predicted using urinary concentrations."

Journal • Overactive Bladder

Characterization of Chemical Interactions between Clinical Drugs and the Oral Bacterium, Corynebacterium matruchotii, via Bioactivity-HiTES. (PubMed, ACS Chem Biol) - "As a result, we identified two cryptic metabolites, methylindole-3-acetate (MIAA) and indole-3-acetic acid (IAA), elicited by imidafenacin, a urinary antispasmodic drug approved by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA)...Unexpectedly, we also found that C. matruchotii metabolized fludarabine phosphate, a USFDA-approved anticancer drug, to 2-fluoroadenine which displayed moderate antibacterial activity against both Bacillus subtilis and Escherichia coli, with IC50 values of 8.9 and 20.1 μM, respectively. Finally, acelarin, a prodrug of the anticancer drug gemcitabine, was found to exhibit unreported antibacterial activity against B. subtilis with an IC50 value of 33.6 μM through the bioactivity-HiTES method as well. These results indicate that bioactivity-HiTES can also be applied to discover biotransformed products in addition to finding cryptic metabolites in microbes."

Journal • Oncology • Pulmonary Disease • Respiratory Diseases

Comparison of add-on medications for persistent storage symptoms after α-blocker treatment in BPH patients - a network meta-analysis. (PubMed, BMC Urol) - "BPH patients presenting with persistent storage symptoms despite α-blocker administration are recommended to include additional treatment. Desmopressin and imidafenacin may be considered high-priority add-on treatments because of their superior efficacy compared with other medications."

Journal • Retrospective data • Review • Benign Prostatic Hyperplasia

Comparative assessment of efficacy and safety of approved oral therapies for overactive bladder: a systematic review and network meta-analysis. (PubMed, Int Braz J Urol) - "Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety."

Journal • Retrospective data • Review • Cardiovascular • Constipation • Gastroenterology • Gastrointestinal Disorder • Hypertension • Infectious Disease • Nephrology • Overactive Bladder • Pain • Xerostomia

Oral anticholinergic drugs versus placebo or no treatment for managing overactive bladder syndrome in adults. (PubMed, Cochrane Database Syst Rev) - "The use of anticholinergic drugs by people with overactive bladder syndrome results in important but modest improvements in symptoms compared with placebo treatment. In addition, recent studies suggest that this is generally associated with only modest improvement in quality of life. Adverse effects were higher with all anticholinergics compared with placebo. Withdrawals due to adverse effects were also higher for all anticholinergics except tolterodine. It is not known whether any benefits of anticholinergics are sustained during long-term treatment or after treatment stops."

Journal • Review • Overactive Bladder • Urinary Incontinence • Xerostomia

Efficacy and safety of vibegron compared with mirabegron for overactive bladder: A systematic review and network meta-analysis. (PubMed, Low Urin Tract Symptoms) - "Both drugs seem to be comparable and well tolerated, particularly as direct comparisons are not available. However, vibegron may be more effective than mirabegron in reducing mean voided volume."

Journal • Retrospective data • Review • Cardiovascular • Infectious Disease • Overactive Bladder

Choosing the Most Efficacious and Safe Oral Treatment for Idiopathic Overactive Bladder: A Systematic Review and Network Meta-analysis. (PubMed, Eur Urol Focus) - "Taken together, there is only minimal difference between the efficacy of oral antimuscarinics and that of β-adrenoceptor agonists. Although finding the best medication for all is impossible, finding the best treatment for every individual patient can be done by considering the efficacy of a medicine for the most bothersome symptom(s) in balance with drug-specific adverse events."

Journal • Retrospective data • Review • Gastrointestinal Disorder • Overactive Bladder • Urinary Incontinence • Urology

Comparisons of the therapeutic safety of seven oral antimuscarinic drugs in patients with overactive bladder: a network meta-analysis. (PubMed, J Int Med Res) - "Tolterodine may be preferable as it showed a reduced association with important AEs. Darifenacin, fesoterodine, imidafenacin, oxybutynin, and solifenacin have similar safety profiles in treating patients with OAB. Taken together, this analysis provides a valuable overview of the therapeutic safety for oral antimuscarinic drugs and is useful for personalized medicine in patients with OAB.Trial registration: This trial was retrospectively registered at INPLASY (https://inplasy.com/) with the registration number 202170095."

Clinical • Journal • Retrospective data • Constipation • Dry Eye Disease • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Nephrology • Ophthalmology • Overactive Bladder • Xerostomia

A systematic review of neurocognitive dysfunction with overactive bladder medications. (PubMed, Int Urogynecol J) - "In this review, cognitive decline was reported with oxybutynin and tolterodine use and should be used with caution in adults over 65 years of age. Solifenacin, fesoterodine, and imidafenacin showed mixed results related to central nervous system effect. Trospium and darifenacin were not associated with cognitive decline among patients with and without baseline cognitive impairment."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Diabetes • Metabolic Disorders • Overactive Bladder

Urinary reabsorption in the rat kidney by anticholinergics. (PubMed, Sci Rep) - "The absorption rate for 2 h was examined following the intravenous administration of the anticholinergics imidafenacin (IM), atropine (AT), and tolterodine (TO)...Anticholinergics or 1-deamino-[8-D-arginine]-vasopressin (dDAVP) were intravenously administered...The urinary reabsorption mechanism through the bladder epithelium was not activated by anticholinergic administration. Thus, anticholinergics suppress urine production via an increase in urine reabsorption in the kidneys' collecting duct cells via AQP2."

Journal • Preclinical • Anesthesia • Overactive Bladder

Triple Therapy with Tamsulosin, Dutasteride, and Imidafenacin for Benign Prostatic Hyperplasia in Patients with Overactive Bladder Symptoms Refractory to Tamsulosin: Subgroup Analyses of the DIrecT Study. (PubMed, Urol Int) - "Triple therapy with TDI is suggested to be a therapeutic option for benign prostatic hyperplasia in patients with residual OAB symptoms refractory to tamsulosin and in patients with various background characteristics regardless of severity of OAB symptoms. Trial Registry No. UMIN 000011980."

Clinical • Journal • Benign Prostatic Hyperplasia • Overactive Bladder

Meta-Analysis of the Efficacy and Safety of Imidafenacin for Overactive Bladder Induced by Benign Prostatic Hyperplasia in Men Receiving Alpha-Blocker Therapy. (PubMed, Int Neurourol J) - "This study suggested that imidafenacin plus alpha-blocker was an efficacious and safe treatment for OAB symptoms in BPH patients."

Journal • Retrospective data • Benign Prostatic Hyperplasia • Overactive Bladder

Persistence and Adherence of Anticholinergics and Beta-3 Agonist for the Treatment of Overactive Bladder: Systematic Review and Meta-Analysis, and Network Meta-Analysis. (PubMed, J Urol) - "Persistence and adherence rates were lower than previously reported and were associated with certain clinical and demographic factors."

Journal • Retrospective data • Review • Overactive Bladder

"Aupa los maduritos! 💪🏼" (@Curro_Blanco)

Mitochondria modulate programmed neuritic retraction. (PubMed, Proc Natl Acad Sci U S A) - "...This is a controlled process that may not lead to neuronal death and, thus, we term this phenomenon "neuritosis." Consistent with our hypothesis, we show that in primary cerebrocortical neurons, mitochondrial distance from the soma correlates with increased mitochondrial protein damage, PINK1 accumulation, reactive oxygen species production, and decreased mitochondrial membrane potential and depolarization threshold. Furthermore, we demonstrate that the distance-dependent mitochondrial membrane potential gradient exists in vivo in mice. We demonstrate that impaired distal mitochondria have a lower threshold for focal/nonlethal neuritic caspase-3 activation in normal neurons that is exacerbated in aging, stress, and neurodegenerative conditions, thus delineating a fundamental mechanistic underpinning for synaptic vulnerability."

Journal