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Pharmaceutics May 2020Polymer-drug conjugates are currently being more widely investigated for the treatment of hypertension. In view of the above, in the first stage of our work, we used...
Polymer-drug conjugates are currently being more widely investigated for the treatment of hypertension. In view of the above, in the first stage of our work, we used nontoxic β-cyclodextrin (β-CD) as effective, simple, inexpensive, and safe for the human body initiator for the synthesis of biocompatible and biodegradable functionalized polymers suitable for the medical and pharmaceutical applications. The obtained polymeric products were synthesized through a ring-opening polymerization (ROP) of ε-caprolactone (CL), d,l-, and l,l- lactide (LA and LLA). The chemical structures of synthesized materials were elucidated based on H NMR and solid-state carbon-13 cross-polarization/magic angle spinning nuclear magnetic resonance (C CP/MAS NMR) analysis, while the incorporation of β-CD molecule into the polymer chain was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Furthermore, molecular modeling has been applied to investigate the intrachain rigidities and chain architectures for several representative structures. The obtained and thoroughly characterized branched matrices were then used to generate the first β-cyclodextrin/biodegradable polymer/β-blocker conjugate through the successful conjugation of pindolol. The conjugates were fabricated by carbodiimide-mediated coupling reaction. The branched biodegradable materials released the drug in vitro in a sustained manner and without "burst release" and thus have the ability to treat different heart diseases.
PubMed: 32486203
DOI: 10.3390/pharmaceutics12060500 -
Journal of Ethnopharmacology Oct 2020Ziziphus mucronata (ZM) is used traditionally in the treatment of mood and depression. However, no existing scientific data is confirming this traditional claim.
Anxiolytic and antidepressant effects of Ziziphus mucronata hydromethanolic extract in male rats exposed to unpredictable chronic mild stress: Possible mechanisms of actions.
ETHNOPHARMACOLOGICAL RELEVANCE
Ziziphus mucronata (ZM) is used traditionally in the treatment of mood and depression. However, no existing scientific data is confirming this traditional claim.
AIM OF THE STUDY
The present study was planned to investigate the anxiolytic and antidepressant-like effects of this plant in a stressed-induced depression model in rats.
MATERIALS AND METHODS
Depressive-like behaviors were induced by exposing rats to different stress paradigms daily for 30 days. A sucrose preference test was performed to assess anhedonia in rats. Anxiety and depression-related behavior were assessed. The oxidative parameters (lipid peroxidation, SOD and catalase activities) were evaluated. Pindolol and Flumazenil were also used to assess the mechanism of action of ZM extract.
RESULTS
The results showed that chronic administration of ZM (150, 300, and 600 mg/kg, p.o., 30 days) and imipramine treatment (20 mg/kg, p.o, 30 days) remarkably (P < 0.05) reversed the UCMS-induced behavioral changes observed in stress vehicle treated rats by reducing sucrose preference, decreased the immobility period in the FST and latency in NSF. Besides, ZM (300 and 600 mg/kg, p.o., 30 days) raised the percentages of time spent and number of open arms entries as well as the number of transitions. Also, ZM (300 mg/kg, (P < 0.05) decreased lipid peroxidation and increased both SOD and catalase activities (300 and 600 mg/kg, (P < 0.05)). These aforementioned behavioral indices were also completely nullified by pindolol a β-adrenoceptors blocker and 5-HT 1A/1B receptor antagonist but not by flumazenil, a benzodiazepine receptors antagonist.
CONCLUSION
ZM improved symptoms of anxiety and depression in behavioral despair paradigm in chronically stressed rats. The observed effects could be due to its capacities to restore the antioxidant status, and probably the modulation of monoamines transmissions.
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Antioxidants; Anxiety; Behavior, Animal; Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Lipid Peroxidation; Male; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Stress, Psychological; Ziziphus
PubMed: 32446929
DOI: 10.1016/j.jep.2020.112987 -
Psychiatry Investigation Jan 2019Treatment for panic disorder (PD) have evolved, although there is still a strong unmet need for more effective and tolerable options. The present study summarizes and...
OBJECTIVE
Treatment for panic disorder (PD) have evolved, although there is still a strong unmet need for more effective and tolerable options. The present study summarizes and discusses recent evidence regarding the pharmacological and neuromodulatory treatment of PD.
METHODS
MEDLINE, Cochrane Library, PsycINFO and Thomson Reuters's Web of Science were searched for clinical trials published between 2010 and 2018. We included all prospective experimental studies including randomized controlled trials (RCT) and other clinical trials with more than 10 patients.
RESULTS
Only 11 articles met the inclusion criteria, including 4 RCT, 3 open clinical trials and 5 comparative clinical trials. RCT demonstrated efficacy of transcranial magnetic stimulation (TMS) in only one of two trials. Neither pindolol nor d-fenfluramine were effective in blocking flumazenil-induced panic attacks. Augmentation with quetiapine was not superior to placebo. Open trials indicated that escitalopram, vortioxetine and TMS may be effective. Comparative trials did not demonstrate superiority from any drug, but confirmed tranylcypromine, paroxetine, clonazepam and alprazolam as effective options.
CONCLUSION
The current study confirmed the efficacy of tranylcypromine, paroxetine, clonazepam, alprazolam and escitalopram. Vortioxetine and TMS, with duration of 4 or more weeks, also seems to be effective. Quetiapine, pindolol and d-fenfluramine were not considered effective compounds.
PubMed: 30696238
DOI: 10.30773/pi.2018.12.21.1 -
International Journal of Molecular... Sep 2020Several research disciplines require fast, reliable and highly automated determination of pharmaceutically active compounds and their enantiomers in complex biological...
Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems.
Several research disciplines require fast, reliable and highly automated determination of pharmaceutically active compounds and their enantiomers in complex biological matrices. To address some of the challenges of Capillary Electrophoresis (CE), such as low concentration sensitivity and performance degradation linked to the adsorption and interference of matrix components, CE in a hydrodynamically closed system was evaluated using the model compounds Pindolol and Propranolol. Some established validation parameters such as repeatability of injection efficiency, resolution and sensitivity were used to assess its performance, and it was found to be broadly identical to that of hydrodynamically opened systems. While some reduction in separation efficiency was observed, this was mainly due to dispersion caused by injection and it had no impact on the ability to resolve enantiomers of model compounds even when spiked into complex biological matrix such as blood serum. An approximately 18- to 23-fold increase in concentration sensitivity due to the employment of wide bore capillaries was observed. This brings the sensitivity of CE to a level similar to that of liquid chromatography techniques. In addition to this benefit and unlike in hydrodynamically opened systems, suppression of electroosmotic flow, which is essential for hydrodynamically closed systems practically eliminates the matrix effects that are linked to protein adsorption.
Topics: Electrophoresis, Capillary; Hydrodynamics; Pharmaceutical Preparations; Pindolol; Propranolol; Reproducibility of Results; Sensitivity and Specificity; Serum; Software; Stereoisomerism
PubMed: 32961980
DOI: 10.3390/ijms21186852 -
Frontiers in Oncology 2022Beta-blockers are currently studied to improve therapeutic options for patients with angiosarcoma. However, most of these patients have no cardiovascular co-morbidity...
Beta-blockers are currently studied to improve therapeutic options for patients with angiosarcoma. However, most of these patients have no cardiovascular co-morbidity and it is therefore crucial to discuss the most optimal pharmacological properties of beta-blockers for this population. To maximize the possible effectiveness in angiosarcoma, the use of a non-selective beta-blocker is preferred based on data. To minimize the risk of cardiovascular adverse events a beta-blocker should ideally have intrinsic sympathomimetic activity or vasodilator effects, e.g. labetalol, pindolol or carvedilol. However, except for one case of carvedilol, only efficacy data of propranolol is available. In potential follow-up studies labetalol, pindolol or carvedilol can be considered to reduce the risk of cardiovascular adverse events.
PubMed: 36185303
DOI: 10.3389/fonc.2022.940582 -
Nanomaterials (Basel, Switzerland) Nov 2022Water pollution is a significant issue nowadays. Among the many different technologies for water purification, photocatalysis is a very promising and...
Water pollution is a significant issue nowadays. Among the many different technologies for water purification, photocatalysis is a very promising and environment-friendly approach. In this study, the photocatalytic activity of SrLaTiO (SLTO) and SrCaNaPrTiO (SCNPTO) nano-sized powders were evaluated by degradation of pindolol in water. Pindolol is almost entirely insoluble in water due to its lipophilic properties. The synthesis of the SCNPTO was performed using the reverse co-precipitation method using nitrate precursors, whereas the SLTO was produced by spray pyrolysis (CerPoTech, Trondheim Norway). The phase purity of the synthesized powders was validated by XRD, while HR-SEM revealed particle sizes between 50 and 70 nm. The obtained SLTO and SCNPTO powders were agglomerated but had relatively similar specific surface areas of about 27.6 m g and 34.0 m g, respectively. The energy band gaps of the SCNPTO and SLTO were calculated (DFT) to be about 2.69 eV and 3.05 eV, respectively. The photocatalytic performances of the materials were examined by removing the pindolol from the polluted water under simulated solar irradiation (SSI), UV-LED irradiation, and UV irradiation. Ultra-fast liquid chromatography was used to monitor the kinetics of the pindolol degradation with diode array detection (UFLC-DAD). The SLTO removed 68%, 94%, and 100% of the pindolol after 240 min under SSI, UV-LED, and UV irradiation, respectively. A similar but slightly lower photocatalytic activity was obtained with the SCNPTO under identical conditions, resulting in 65%, 84%, and 93% degradation of the pindolol, respectively. Chemical oxygen demand measurements showed high mineralization of the investigated mixtures under UV-LED and UV irradiation.
PubMed: 36500815
DOI: 10.3390/nano12234193 -
European Journal of Clinical... Oct 2014Dose modification in renal impairment has traditionally been based on changes in estimated glomerular filtration rate (eGFR; estimated by creatinine clearance). However,...
PURPOSE
Dose modification in renal impairment has traditionally been based on changes in estimated glomerular filtration rate (eGFR; estimated by creatinine clearance). However, many drugs are eliminated by tubular anionic and cationic transport where changes in eGFR may not necessarily reflect changes in tubular function. This study investigated the relationship between GFR and renal tubular function with reference to drug handling by using accepted drug probes.
METHODS
Three drug probes, (51)Cr-EDTA, fluconazole, and pindolol, were administered to patients who had varying degrees of renal impairment. Blood sampling, assays, and a pharmacokinetic analysis were performed for all drug probes and endogenous urate. Measured GFR ((51)Cr-EDTA clearance; mGFR) was compared to tubular anionic transport (urate clearance), tubular reabsorption (fluconazole clearance), and tubular cationic transport (S-pindolol clearance).
RESULTS
A moderately strong association was demonstrated between the measured isotopic GFR and creatinine clearance (R(2) = 0.78). A moderate positive correlation was found between mGFR and proximal tubular anion transport and reabsorption (R(2) = 0.40-0.44, p < 0.0001). In contrast, cationic secretion correlated poorly with mGFR (R(2) = 0.11, p = 0.036).
CONCLUSIONS
Given that drug dosing schedules utilise eGFR values as the basis for modifying drug dosing, our results would suggest that a recommendation of a dose reduction according to eGFR alone should be treated with caution.
Topics: Adult; Aged; Aged, 80 and over; Biological Transport; Dose-Response Relationship, Drug; Edetic Acid; Female; Fluconazole; Glomerular Filtration Rate; Humans; Kidney Function Tests; Kidney Tubules, Proximal; Male; Middle Aged; Pindolol; Renal Insufficiency
PubMed: 25135059
DOI: 10.1007/s00228-014-1733-7 -
Journal of Clinical Pharmacology Nov 2020
Topics: Administration, Oral; Antihypertensive Agents; Diuretics; Drug Interactions; Female; Furosemide; Humans; Hypertension; Parturition; Pindolol; Pregnancy; Pregnancy Complications; Stereoisomerism
PubMed: 32789919
DOI: 10.1002/jcph.1719 -
The Journal of Clinical Psychiatry Apr 2015The majority of depressed patients do not experience sufficient response to their initial antidepressant medication. Augmentation strategies, particularly the use of...
The majority of depressed patients do not experience sufficient response to their initial antidepressant medication. Augmentation strategies, particularly the use of atypical antipsychotics to augment selective serotonin reuptake inhibitors (SSRIs), have proliferated over the last 15 years, and 2 atypical antipsychotics, aripiprazole and quetiapine, have received US Food and Drug Administration approval for adjunctive therapy in treatment-resistant depression. Alternatively, data in treatment-resistant depression exist for most of the atypicals and for other treatments, including lithium, bupropion, methylphenidate, pindolol, and buspirone.
Topics: Antidepressive Agents; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Female; Humans; Male; Patient Acceptance of Health Care
PubMed: 25919851
DOI: 10.4088/JCP.14com09586 -
The Science of the Total Environment Jun 2024Pindolol (PIN) is a commonly used β-blocker drug and has been frequently detected in various natural waters. Comprehensive understanding of its environmental...
Pindolol (PIN) is a commonly used β-blocker drug and has been frequently detected in various natural waters. Comprehensive understanding of its environmental photochemical transformation is necessary to assess its environmental risk. In this study, the photodegradation kinetics and mechanisms of PIN in both freshwater and coastal water were investigated for the first time. The photodegradation experiments were carried out by steady-state photochemical experiment under simulated sunlight irradiation. The results showed that the photodegradation rate of PIN in the freshwater of the Pearl River estuary was significantly faster than that in its downstream coastal water. In river water, PIN can undergo both direct photolysis and indirect photolysis induced by riverine dissolved organic matter (DOM) mainly through excited triplet-state of DOM and singlet oxygen, while direct photolysis dominated its degradation in coastal water. The promotion effect was found to be much greater for Suwannee River Natural Organic Matter (SRNOM) than that of the sampled riverine DOM, due to its high steady-state concentrations of reactive species. Interestingly, coastal DOM in northern and southern China were found to have similar promotion effects on PIN photodegradation for the first time, but both less than that of riverine DOM. A total of seven degradation products of PIN resulting from hydroxylation, hydrogen abstraction and cleavage of ether bond were identified. 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.
PubMed: 38582123
DOI: 10.1016/j.scitotenv.2024.172236