Zaichang (naftopidil) / Simcere - LARVOL DELTA

Silodosin in treating men With BPH-associated lower urinary tract Symptoms: A systematic review and network meta-analysis. (PubMed, Int J Surg) - "Silodosin is highly effective for BPH-LUTS, particularly for voiding symptoms, but carries a elevated risk of ejaculatory dysfunction. Combination with tadalafil may enhance urinary flow. Clinicians should weigh efficacy against adverse events; further trials are needed to confirm long-term benefits."

Journal • Retrospective data • Benign Prostatic Hyperplasia

Targeting UGT2B15 and NR1H4 interaction: a novel therapeutic strategy for polycystic ovary syndrome using naftopidil enantiomers. (PubMed, J Ovarian Res) - "UGT2B15 represents a promising target for novel PCOS therapies by modulating androgen metabolism and protecting ovarian granulosa cells from apoptosis. (R)-NAF and (S)-NAF regulate UGT2B15 by disrupting NR1H4's binding to its promoter, implying potential therapeutic compounds for PCOS treatment."

Journal • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Obesity • Polycystic Ovary Syndrome • UGT2B15

Association between alpha blocker use and the risk of fractures in patients with chronic kidney disease: a cohort study. (PubMed, BMC Nephrol) - "AB use in patients with CKD did not increase the risk of fractures when used for the treatment of HT; however, it increased the risk of fractures when used for the treatment of VD in females. These results suggest that ABs should be used with caution in these patients."

Journal • Cardiovascular • Chronic Kidney Disease • Hypertension • Musculoskeletal Diseases • Nephrology • Orthopedics • Renal Disease

Comparative efficacy and safety of alpha-blockers as monotherapy for benign prostatic hyperplasia: a systematic review and network meta-analysis. (PubMed, Sci Rep) - "IPSS has been considerably improved by tamsulosin 0.4 mg, naftopidil 50 mg and silodosin 8 mg as compared to the placebo. Based on the p-score, tamsulosin 0.4 mg had the highest probability of ranking for IPSS, PVR, and Qmax, whereas doxazosin 8 mg had the highest probability of improving QoL...Current evidence supports α-blockers are effective in IPSS reduction and are considered safer. Larger sample size with long-term studies are needed to refine estimates of IPSS, QoL, PVR, and Qmax outcomes in α-blocker users."

Clinical • Journal • Monotherapy • Retrospective data • Review • Benign Prostatic Hyperplasia

Comparative Efficacy and Safety of Alpha-Blockers As Monotherapy for Benign Prostatic Hyperplasia: A Systematic Review and Network Meta-Analysis (ISPOR 2024) - "Compared with the placebo, tamsulosin 0.4 mg (SMD: -6.10; 95% CI: [-8.74; -3.47]), followed by naftopidil 50mg (SMD: -5.09; 95% CI: [ -8.29; -1.89]) and silodosin 8mg has significantly improved IPSS. Pairwise comparisons indicate that doxazosin 8mg improves QoL, and tamsulosin 0.4 mg reduces PVR and Qmax compared to placebo... Current evidence suggested α-blockers are beneficial for BPH, with tamsulosin 0.4 mg being the most effective and are usually safe as first-line therapy. A larger sample size along with long-term studies are required to refine our estimates of IPSS, QoL, PVR, and Qmax among α-blocker users."

Monotherapy • Retrospective data • Review • Benign Prostatic Hyperplasia

Ligated Pd-Catalyzed Aminations of Aryl/Heteroaryl Halides with Aliphatic Amines under Sustainable Aqueous Micellar Conditions. (PubMed, JACS Au) - "Applications involving highly challenging reaction partners constituting late-stage functionalization are documented, as is a short but efficient synthesis of the drug naftopidil. Comparisons with existing aminations highlight the many advances being offered."

Journal

Characteristics of α1 -adrenoceptor antagonists-induced ejaculatory dysfunction on spontaneous seminal emission in rats. (PubMed, Basic Clin Pharmacol Toxicol) - "In the spontaneous seminal emission (SSE) test, systemically administered prazosin, terazosin, tamsulosin and naftopidil decreased the weight of ejaculated seminal material in a dose-dependent manner; the potency order was as follows: tamsulosin > terazosin > prazosin > naftopidil. These results indicated that the difference in inhibitory potency of the five α1 -AR antagonists against SSE was due to the involvement of α1A -AR subtypes. Our results further suggested that α1 -AR antagonist-induced ejaculatory dysfunction at the peripheral level was mainly due to the loss of seminal emission, although some retrograde ejaculation may also be involved."

Journal • Preclinical • Benign Prostatic Hyperplasia

Comparative Efficacy and Safety of Alpha-Blockers as Single Agent for Benign Prostatic Hyperplasia: A Systematic Review and Network Meta-Analysis (ISPOR-EU 2023) - "Compared with the placebo, tamsulosin 0.4 mg (SMD: -6.10; 95% CI: [-8.74; -3.47]), followed by naftopidil 50mg (SMD: -5.09; 95% CI: [ -8.29; -1.89]) and silodosin 8mg (SMD: -3.63; 95% CI: [- 6.31; -0.95]) has significantly improved IPSS. According to the pairwise comparisons, doxazosin 8mg (-1.35 [-4.68; 1.98]) improves the QoL compared to placebo... Current evidence suggested α-blockers are beneficial for BPH, with tamsulosin 0.4 mg being the most effective and are usually safe as first-line therapy, with relatively few AEs."

Retrospective data • Review • Benign Prostatic Hyperplasia • Hypotension

Development of an In Vitro Methodology to Assess the Bioequivalence of Orally Disintegrating Tablets Taken without Water. (PubMed, Pharmaceutics) - "The values of the f2 function in permeation profiles of pitavastatin and memantine ODTs were both 62 when the optimized experimental settings for naftopidil formulations were applied. This methodology can be useful in formulation studies for estimating the BE probability between ODTs and CTs."

Journal • Preclinical • Gastrointestinal Disorder

Association of silodosin, tamsulosin, and naftopidil with delirium: analysis of the pharmacovigilance database in Japan. (PubMed, Int J Clin Pharm) - "Anticholinergics or beta3-adrenergic receptor agonists to treat overactive bladder in patients receiving tamsulosin and naftopidil was strongly associated with delirium. Confirming the medical history and concomitant medications of patients receiving tamsulosin or naftopidil may contribute to preventing delirium in patients with benign prostatic hyperplasia and to improving their outcomes."

Adverse events • Journal • Benign Prostatic Hyperplasia • CNS Disorders • Overactive Bladder

Relative Efficacy and Safety of Alpha-Blockers As Monotherapy in Men with Benign Prostatic Hyperplasia: A Systematic Review and Network Meta-Analysis (ISPOR 2023) - "Compared with the placebo, tamsulosin 0.4 mg (SMD: -6.31; 95% CI: [-10.05; -2.57]), naftopidil 50mg (SMD: -5.17; 95% CI: [-9.76; -0.58]) and silodosin 8mg (SMD: -3.84; 95% CI: [-7.72; 0.04]) has significantly reduced international prostate symptom score (IPSS). According to the pairwise comparison, doxazosin 8mg (SMD: -1.35; 95% CI: [-4.68; 1.98]) improved the quality of life (QoL)... Generated evidence suggests that α-blockers are beneficial for BPH, tamsulosin being the most effective and comparatively safe as first-line therapy, with relatively few AEs."

Monotherapy • Retrospective data • Review • Benign Prostatic Hyperplasia • Hypotension

Efficacy And Safety Study Of Naftopidil to Patients Treatment With LUTS (clinicaltrials.gov) - P3 | N=0 | Withdrawn | Sponsor: Apsen Farmaceutica S.A. | N=250 ➔ 0 | Unknown status ➔ Withdrawn

Enrollment change • Trial withdrawal • Benign Prostatic Hyperplasia

Effect of α1D-adrenoceptor blocker for the reduction of ureteral contractions. (PubMed, Investig Clin Urol) - "We studied the effects of naftopidil, an α1D-AR inhibitor, on the ureter. Compared with alpha-blockers, naftopidil significantly relaxed ureteral smooth muscle. Therefore, naftopidil could be an effective therapy for patients with ureteral stones."

Journal • Renal Calculi • Urolithiasis

Inhibition of Liquid-Liquid Phase Separation for Breaking the Solubility Barrier of Amorphous Solid Dispersions to Improve Oral Absorption of Naftopidil. (PubMed, Pharmaceutics) - "Although the dissolution behavior of the Eudragit ASD was found to be markedly poorer than that of other ASDs, it offered the best oral absorption in rats. The findings of the current study highlight the possibility for improving the oral absorption of poorly soluble drugs by this ASD, which should be eliminated from candidate formulations based on the conventional in vitro tests."

Journal

Effect of alpha-adrenoceptor antagonists on sexual function. A systematic review and meta-analysis. (PubMed, Arch Ital Urol Androl) - "Silodosin was associated with increased odds of ejaculatory dysfunction compared with tamsulosin (OR: 3.52, 95% CI: 2.18-5.68, 15 series, 1512 participants, Z = 5.15, p < 0.00001, I2 = 0%). Naftopidil and alfuzosin showed lower odds of ejaculatory dysfunction compared to uroselective alpha-blockers.No statistically significant differences in the odds of erectile dysfunction were observed when alpha-blockers were compared to placebo."

Journal • Retrospective data • Review • Benign Prostatic Hyperplasia • Cardiovascular • Erectile Dysfunction • Hypertension • Renal Calculi • Sexual Disorders

The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study. (PubMed, Appl Biochem Biotechnol) - "2-{[4-(2-Methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles, their 5 substituted derivatives, and structurally similar, arylpiperazine based alpha1-adrenergic receptors antagonists (trazodone, naftopidil, and urapidil) have been subjects of comparative analysis. The in silico docking and molecular dynamics simulations, binding data together with absorption, distribution, metabolism, and excretion (ADME) calculations identified the promising lead compounds. The results brought out the conclusions which allowed us to propose a rationale for the activity of these molecules and to highlight six compounds (2-5, 8, and 12) that exhibited an acceptable pharmacokinetic profile to the advanced investigation as the potential alpha1-adrenergic receptor antagonists."

Journal • Preclinical • Asthma • Atrial Fibrillation • Benign Prostatic Hyperplasia • Cardiovascular • CNS Disorders • Congestive Heart Failure • Depression • Endocrine Disorders • Heart Failure • Hypertension • Immunology • Psychiatry • Pulmonary Disease • Respiratory Diseases • ADRA1B

Naftopidil enantiomers suppress androgen accumulation and induce cell apoptosis via the UDP-glucuronosyltransferase 2B15 in benign prostate hyperplasia. (PubMed, J Steroid Biochem Mol Biol) - "Together, our results demonstrated that NAF enantiomers could be potential and novel UGT2B15 regulators, which accelerated the DHT elimination and promoted apoptosis of BPH-1 cells. This study could help expand the clinical application of NAF and support the development of new therapeutic strategies targeting the elimination of androgens for the treatment of BPH and other androgen-sensitive diseases."

Journal • Benign Prostatic Hyperplasia • Urology • AR • KLK3 • UGT2B15

Fluorobenzoic acid coformers to improve the solubility and permeability of the BCS class IV drug naftopidil. (PubMed, Chem Commun (Camb)) - "Crystalline salts of the low solubility and low permeability drug naftopidil were investigated with mono-, di-, tri-, and tetrafluorobenzoic acids as coformers to show that 245TFBA (2,4,5-trifluorobenzoic acid) is the optimal salt with faster dissolution and high permeability, thereby opening the study of fluorinated coformers in pharmaceutical cocrystals and salts."

Journal

The affinity and selectivity of α-adrenoceptor antagonists, antidepressants and antipsychotics for the human α2A, α2B, and α2C-adrenoceptors and comparison with human α1 and β-adrenoceptors. (PubMed, Pharmacol Res Perspect) - "A few α-ligands with significant β-affinity were detected, for example, naftopidil where its clinical α1A-affinity is only 3-fold greater than off-target β2-affinity. Antidepressants (except mirtazapine) and first-generation antipsychotics have higher α1A than α2-adrenoceptor affinity but poor β-affinity...Risperidone (9 nM) and paliperidone (14 nM) have the highest α2C-adrenoceptor affinity however this is only 5-fold selective over α2A, and both have a higher affinity for α1A (2 nM and 4 nM, respectively). So, despite a century of yohimbine use, and decades of α2-subtype studies, there remains plenty of scope to develop α2-subtype selective antagonists."

Journal • Anesthesia • CNS Disorders • Hypertension

The efficacy and safety of alpha-adrenergic blockers for medical expulsion therapy in patients with ureteral calculi: A meta-analysis of placebo-controlled trials. (PubMed, Medicine (Baltimore)) - "Although α-blockers cannot improve the overall ureteral stone clearance rate, these drugs are still effective for the treatment of stones in the distal urinary tract. However, the application of α-blockers is likely to cause dizziness and/or retrograde ejaculation."

Journal • Retrospective data • Renal Calculi • Urolithiasis • Urology

Analyses of the Mode of Action of an Alpha-Adrenoceptor Blocker in Substantia Gelatinosa Neurons in Rats. (PubMed, Int J Mol Sci) - "Third, the highest concentration of naftopidil (100 μM) led to two types of response in the SG neurons, which corresponded with the reactions to 5-HT and prazosin. These results indicate that not all neurons were necessarily activated by naftopidil, and that the micturition reflex may be regulated in a sophisticated manner by inhibitory mechanisms in these interneurons."

Journal • Preclinical

Editorial Comment to Comparison of disease-specific quality of life in prostate cancer patients treated with low-dose-rate brachytherapy: A randomized controlled trial of silodosin versus naftopidil. (PubMed, Int J Urol) - No abstract available

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

Bioequivalence of Oral Drug Products in the Healthy and Special Populations: Assessment and Prediction Using a Newly Developed In Vitro System "BE Checker". (PubMed, Pharmaceutics) - "Dipyridamole, a basic drug, showed rapid and supersaturated dissolution when the paddle speed in the donor chamber was 200 rpm, which corresponds to the high agitation strength in the stomach...To investigate that those factors also affect the BE of oral drug products, dissolution and permeation of naftopidil from its ordinary and orally disintegrating (OD) tablets were observed in the BE checker...These results indicated the possibility of the bioinequivalence of some oral formulations in special patients whose GI physiologies are different from those in the healthy subjects. The BE checker can be a highly capable in vitro tool to assess the BE of oral drug products in various populations."

Journal • Preclinical • Gastrointestinal Disorder

Cutoff level of prostate volume to predict the efficacy of α1-D/A adrenoceptor antagonist, naftopidil. (PubMed, Urol Ann) - "The best standard value to evaluate the efficacy IPSS-VS at 4 weeks was 4 points for the NAF treatment, and the best PV cutoff point was 37.3 mL (sensitivity 60.5%, specificity 71.9%). PV at baseline was one of the predictive factors which affected the efficacy of NAF for IPSS-VS, and LUTS/BPH patients who had PV more than 37.3 mL indicated poor improvement of IPSS-VS, even if IPSS-TS was improved."

Clinical • Journal • Benign Prostatic Hyperplasia

Comparison of disease-specific quality of life in prostate cancer patients treated with low-dose-rate brachytherapy: A randomized controlled trial of silodosin versus naftopidil. (PubMed, Int J Urol) - "Naftopidil and silodosin provide different disease-specific quality of life outcomes in patients undergoing, especially in terms of bowel function and sexual bother. These findings can help in the selection of α-1 adrenoceptor antagonists after low-dose-rate brachytherapy."

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