Visken (pindolol) / Novartis - LARVOL DELTA

Cachexia and Wasting in Chronic Illness: Regulatory and Clinical Trial Update. (PubMed, J Cachexia Sarcopenia Muscle) - "In contrast, TCMCB07, an MC-4 receptor antagonist, demonstrated promising results in preclinical and early-phase human studies, showing weight stabilization and improved caloric intake with good tolerability. ART27.13, a dual CB1/CB2 receptor agonist, also demonstrated positive effects in appetite stimulation and weight stabilization. For S-pindolol, which targets appetite and metabolism, Phase IIb/III trials are to be initiated, following an earlier Phase II trial that showed improved muscle mass and muscle strength (hand grip strength). Future treatments must focus on integrating patient-centred goals, therapeutic mechanisms and meaningful clinical outcomes."

Journal • Review • Cachexia • Oncology

Predicting compounds that interact with the 2 known agonist-induced conformations of the human β1-adrenoceptor. (PubMed, Mol Pharmacol) - "Using a structure-activity hypothesis built on the predicted poses CGP12177 and 3 biphasic agonists (alprenolol, oxprenolol, and bucindolol), predictions based on ligand similarity and structural compatibility reasoning were made about 11 other β1-ligands not yet tested for secondary conformation interaction and examined in radioligand binding and functional assays using human β1- and β2-adrenoceptors...Carteolol (related to CGP12177) and bunitrolol (similar to alprenolol) activated both conformations with biphasic concentration responses...In a β1-adrenoceptor mutant (β1-V189T-L195Q-W199Y) where secondary site CGP12177 and pindolol interaction is lost, the 3 novel secondary-site compounds were also no longer able to stimulate secondary conformation responses, suggesting that there is a common TM4 secondary conformation-inducing interaction site. SIGNIFICANCE STATEMENT: The β1-adrenoceptor exists in 2 agonist-stabilized, pharmacologically distinguishable conformations...."

Journal

Nutrition in cachexia: support by pharmacological options? (DGHO 2025) - "According to initial clinical studies there is a group of particularly promising agents, including: the selective androgen enobosarm, S-pindolol, which has a mixed effect on beta receptors, the central appetite stimulant anamorelin, which has been approved in Japan, the cytokine-blocking substances bermekimab (anti-IL1alpha), tocilizumab (anti-IL6) and ruxolitinib (Jak1/2 inhibitor), the atypical neuroleptic olanzapine and newer GDF-15 antibodies such as ponsegromab. For approval, effects on the spectrum of symptoms, performance and body composition will probably be required."

Anorexia • Cachexia • Fatigue • GDF15 • IL1A

BETA-BLOCKERS ARE ASSOCIATED WITH LOWER RISK OF PANCREATIC CANCER IN PATIENTS WITH TYPE 2 DIABETES: A POPULATION-BASED COHORT STUDY (UEGW 2025) - "Primary exposure was beta-blocker use (e.g., acebutotlol, atenolol, bisoprolol, carvedilol, celiprolol, esmolol, labetalol, metoprolol, nadolol, nebivolol, pindolol, propranolol, and sotalol)...Adjusted hazard ratios (aHRs) were derived from multivariable Cox models adjusting for 31 covariates: age, sex, smoking status, alcohol use disorder, body index mass, glycemic control (in terms of time-weighted mean HbA1c), pancreatitis, cholangitis, colectomy, Charlson's comorbidity index, metabolic and cardiovascular comorbidities, and concomitant medications (aspirin, non-steroidal anti-inflammatory drugs, statins, and other antidiabetics)... Beta-blocker use was associated with a lowered risk of PC among patients with newly diagnosed T2D, in a dose- and duration-dependent manner."

Clinical • Addiction (Opioid and Alcohol) • Diabetes • Gastrointestinal Disorder • Hepatology • Metabolic Disorders • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

INTEGRATIVE SYSTEMATIC REVIEW ON PHARMACOLOGICAL, PSYCHOTHERAPEUTIC AND NEUROSTIMULATORY TREATMENT OPTIONS IN TREATMENT-RESISTANT ANXIETY DISORDERS. (PubMed, Psychother Psychosom) - "According to RCTs, selective serotonin reuptake inhibitors (SSRI) or clomipramine are effective in TR-PD after failure to respond to cognitive behavioral therapy (CBT). In pharmacological TR-SAD, switching from one SSRI to another or to venlafaxine was found helpful in open label trials. RCTs further suggest augmentation with quetiapine, risperidone, olanzapine or pregabalin in TR-GAD, pindolol in TR-PD and clonazepam in TR-SAD. Open label studies in TR-AD provide preliminary evidence for ketamine or augmentation with nefazodone, reboxetine, buspirone, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, divalproex sodium, levetiracetam, zonisamide, flumazenil, pregabalin, cannabidiol and acamprosate...Only inconclusive support was identified for repetitive transcranial magnetic stimulation (rTMS) in TR-AD. In summary, this integrative review may provide an evidence base for expert recommendations, inform clinical guidelines, and inspire further research into..."

Journal • Review • CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry • Social Anxiety Disorder

PROACT: A Study of the Effect of (S)-Pindolol Benzoate (ACM-001.1) on Lean Body Mass (LBM) in Obese Patents During, and Post-semaglutide Therapy (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Actimed Therapeutics Ltd

New P2 trial • Genetic Disorders • Obesity

Exploration of low-dose ozone-activated periodate (O₃/IO₄⁻) for rapid degradation of the β-Blocker pindolol: efficiency and radical mechanism. (PubMed, Water Res) - "Zebrafish toxicity experiments showed that the O₃/PI system effectively detoxifies PIN, though the toxicity of intermediates warrants attention. In conclusion, the developed O₃/PI system offers an efficient and environmentally friendly strategy for PI activation and the treatment of emerging organic pollutants such as PIN."

Journal

The Effectiveness of Liquid-Phase Microextraction of Beta-Blockers from Aqueous Matrices for Their Analysis by Chromatographic Techniques. (PubMed, Molecules) - "The aim of this research is to test the effectiveness of two green liquid-phase microextraction procedures, such as dispersive liquid-liquid microextraction (DLLME) and solidification of floating organic droplet microextraction (SFOME) for the selective extraction of eight beta-blockers (atenolol, nadolol, pindolol, acebutolol, metoprolol, bisoprolol, propranolol, and betaxolol) from aqueous matrices for their analysis by gas chromatography (GC) or liquid chromatography (LC). Good limits of detection (0.13 to 0.69 µg/mL for GC and 0.07 to 0.15 µg/mL for HPLC) and limits of quantification (0.39 to 2.10 µg/mL for GC and 0.20 to 0.45 µg/mL for LC) were obtained. The developed procedures were successfully applied to the analysis of selected beta-blockers in wastewater samples, proving their applicability to the real samples."

Journal • Cardiovascular • Hypertension

Pharmacokinetics, Pharmacodynamics and Bioavailability of ACM-001.1 (S-Pindolol Benzoate) in Healthy Volunteers. (PubMed, J Cachexia Sarcopenia Muscle) - P1 | "Data from this bridging study of enantiomerically pure ACM-001.1 and its parent racemic drug, pindolol, support clinical trials of ACM-001.1 for the treatment of cancer cachexia."

Journal • PK/PD data • Cachexia • Fatigue • Oncology • Pain

Pindolol Use for Treatment-Refractory Panic Disorder. (PubMed, Prim Care Companion CNS Disord) - No abstract available

Journal • CNS Disorders • Mood Disorders

Machine learning in obsessive-compulsive disorder medications. (PubMed, Heliyon) - "The ML analysis provided valuable insights into the efficacy of various medications such as clomipramine, duloxetine, and pindolol, as well as supplements such as folate, in the treatment of OCD. Treating concomitant diseases, namely hypothyroidism and streptococcal infection could improve the efficacy of treatment."

Journal • Machine learning • CNS Disorders • Endocrine Disorders • Infectious Disease • Mental Retardation • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate (clinicaltrials.gov) - P2 | N=47 | Completed | Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | N=80 ➔ 47

Enrollment change

UNLOCKING S-PINDOLOL'S POTENTIAL FOR MASLD: BENEFICIAL EFFECTS ON MUSCLE MASS AND FUNCTION AND LIVER HISTOLOGY IN WESTERN-DIET FED MICE (AASLD 2024) - "S- pindolol treatment ameliorates MASLD and enhances muscle quality in WD-fed mice. It may be hypothesized that pindolol's positive effects on muscle mass and function could play a role on its beneficial effects on MASLD through improvement of secretion of various salutary myokines. The present data underscore S-pindolol's therapeutic potential in MASLD."

Preclinical • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Sarcopenia • ACACA • IGF1 • IL10 • TGFB1

BATTLING BETA BLOCKER OVERDOSE: A RACE AGAINST TIME FOLLOWING METOPROLOL OVERDOSE (CHEST 2024) - "Pindolol, a partial agonist, may cause sympathomimetic effects...Hemodialysis may be beneficial in severe cases for those that ingested hydrophilic compounds such as atenolol, nadolol, sotalol, and acebutolol. Lipophilic beta-blockers such as metoprolol, propranolol will not be able to be removed via hemodialysis... Beta- Blockers such as Metoprolol overdose, presents a challenging clinical scenario requiring prompt recognition and aggressive management. Early initiation of supportive measures, including intravenous fluids, vasopressors, and calcium gluconate, along with gastrointestinal decontamination, can significantly reduce morbidity and mortality associated with metoprolol toxicity."

Cardiovascular • CNS Disorders • Congestive Heart Failure • Epilepsy • Gastrointestinal Disorder • Heart Failure • Hypertension • Hypoglycemia • Hypotension

Magnetic particle spray mass spectrometry for the determination of beta-blockers in plasma samples. (PubMed, Mikrochim Acta) - "A dispersive solid phase extraction of atenolol, metoprolol, labetalol, propranolol, nadolol, and pindolol was carried out using magnetic molecularly imprinted polymer (M-MIP) particles that were attached to the tip of a metal probe, which was placed in the mass spectrometer inlet. The method is aligned with green chemistry principles, requiring minimal sample, solvent, and sorbent amounts. MPS-MS successfully integrates sample preparation and ambient ionization mass spectrometry and holds great potential for application with other sorbents, samples, and analytes."

Journal

Cognitive Effects of Three β-Adrenoceptor Acting Drugs in Healthy Volunteers and Patients with Parkinson's Disease. (PubMed, J Parkinsons Dis) - "In Part A, HVs received single doses of 32 mg salbutamol, 160μg clenbuterol, 60 mg pindolol and placebo administered in a randomized, 4-way cross-over study. This study demonstrates the pro-cognitive effects of clenbuterol in HVs with similar trends in PD-patients. The mechanism of action is likely activation of β2-ARs in the CNS."

Journal • Cardiovascular • CNS Disorders • Movement Disorders • Parkinson's Disease

Toxicologic analysis of 35 drugs in post mortem human blood samples with focus on antihypertensive and antiarrhythmic drugs. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "Therefore, a novel analytical method was developed and validated for the quantification of 35 drugs with toxicological relevance, including antihypertensive and antiarrhythmic drugs (ajmaline, amlodipine, amiodarone, atenolol, bisoprolol, carvedilol, clonidine, desethylamiodarone, diltiazem, donepezil, doxazosin, dronedarone, esmolol, flecainide, lercanidipine, lidocaine, metoprolol, nebivolol, nimodipine, pindolol, prajmaline, propafenone, propranolol, sotalol, urapidil, and verapamil), as well as other medications commonly found in combination (sildenafil, tadalafil, atorvastatin, clopidogrel, dapoxetine, memantine, pentoxifylline, rivastigmine, and ivabradine). In addition, the method was specifically tested for the use in post mortem analysis. The applicability of our method was demonstrated by the analysis of two authentic human autopsy blood samples."

Journal

Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate (clinicaltrials.gov) - P2 | N=80 | Completed | Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | Recruiting ➔ Completed | N=134 ➔ 80 | Trial completion date: Feb 2025 ➔ Jun 2024

Enrollment change • Trial completion • Trial completion date

Drugs for hypertension. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Review • Cardiovascular • Hypertension

Evaluation of multitarget drugs on the expression of cocaine-induced locomotor sensitization in male rats: A comparative study. (PubMed, Heliyon) - "Here we compare the efficacy of mirtazapine (MIR), pindolol (PIN), fluoxetine (FLX), risperidone (RIS), trazodone (TRZ), ziprasidone (ZPR), ondansetron (OND), yohimbine (YOH), or prazosin (PRZ), to reduce long-term cocaine-induced locomotor activity and the expression of cocaine-induced locomotor sensitization in rats...After each administration, locomotor activity for each animal was recorded for 30 min.During the agonism phase, in experiment four, 8-OH-DPAT, DOI, CP-809-101, SR-57227A, or clonidine (CLO) was administered 30 min before MIR and 60 min before cocaine...MIR generated a decrease in cocaine-induced locomotor activity of greater magnitude and duration than the other multitarget drugs evaluated. - At the optimal doses of multitarget drugs evaluated, MIR was the multitarget drug that showed the greatest long-term cocaine-induced behavior effects compared to other multitarget drugs."

Journal • Preclinical

Photochemical fate of β-blocker pindolol in riverine and its downstream coastal waters. (PubMed, Sci Total Environ) - "Biological toxicity of one products were found to be higher than that of PIN. These results are of significance for knowing the persistence and ecological risk of PIN in natural waters."

Journal

Electrochemical screening of selected β-blockers at a polarized liquid-liquid interface. (PubMed, Analyst) - "The linear dynamic ranges (LDRs) of the studied β-blockers were in the range of 5-200 μmol L-1 and the lowest limit of detection (LOD) value was determined for pindolol (LOD = 1.96 μM μmol L-1). The latter were compared and correlated with the available literature values of log Poctanol. Finally, a standard addition method was used to determine the concentration of nebivolol in pharmaceutical preparations using a platform based on the electrified liquid-liquid interface."

Journal

Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate (clinicaltrials.gov) - P2 | N=134 | Recruiting | Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | Trial primary completion date: Feb 2024 ➔ Feb 2025

Trial primary completion date

Preparation of a bis-triazolyl bridged β-cyclodextrin stationary phase and its application for enantioseparation of chiral compounds by HPLC. (PubMed, Chirality) - "BCDP could separate a wider range of compounds (53 kinds); especially, some chiral substance pairs that were difficult to be resolved on the ordinary cyclodextrin CSPs, including triazoles containing two chiral carbons (triadimenol, bitertanol, metconazole, and triticonazole), strongly ionized amino acids (acidic Asp, alkalic Arg, and polar Thr) and β-blockers with bulky groups (carvedilol, propranolol, and pindolol). Obviously, the unique synergistic inclusion effect of bridged cyclodextrin with double cavities and the bis-triazole bridging group could provide multiple action sites, such as hydrogen bonding, π-π stacking and acid-base action sites, thus improving its chiral chromatographic performance."

Journal

The "β-Blocker" Carvedilol and Related Aryloxypropanolamines Promote ERK1/2 Phosphorylation in HEK293 Cells with K Values Distinct from their Equilibrium Dissociation Constants as β-Adrenoceptor Antagonists: Evidence for Functional Affinity. (PubMed, J Pharmacol Exp Ther) - "Four, structurally related β-adrenoceptor antagonists (alprenolol, carazolol, pindolol, propranolol) that also activated ERK1/2 were included as comparators to enhance our understanding of how these drugs work in the clinical setting. These data imply that carvedilol and other β-blockers can stabilize the β-adrenoceptor in different affinity conformations that are revealed when functionally distinct responses are measured. This is the basis for the pharmacological concept of "functional affinity"."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure