Alverine Research Articles

Effect of alverine citrate plus simethicone in colonoscopy: a randomized controlled trial.

Colonoscopy is the standard procedure for screening, and surveillance of colorectal cancer, including the treatment for colonic lesions. Colonic spasm is an important problem from colonoscopy that affects both surgeons and patients. The spasm also might be the cause of longer cecal intubation time, difficulty of the procedure, and increased pain. Previous reports indicated that antispasmodic agents can decrease such symptoms. Therefore, we conducted this study to investigate the cecal intubation time of antispasmodic agents. A single blinded randomized controlled trial was conducted from 01/11/2020 to 31/08/2021. One hundred four patients were allocated to antispasmodic agent group and control group, in 1:1 ratio. The efficacy of median (range) cecal intubation time showed similar results of 5 (2, 14) and 5 (2, 15) minutes with no statistically significant difference. The mean scores of all domains i.e., pain, spasm, cleanliness, and difficulty were better in the antispasmodic agent group about 2.6 (1.4), 1.8 (0.8), 2.4 (0.9), and 2.0 (0.9), respectively, than control group but there were spasm and cleanliness showed statistically significant difference. Moreover, the satisfaction scores showed better efficacy in decreased spasm, decreased difficulty, and increased cleanliness than control group. Prescribing of antispasmodic drugs before colonoscopy might be the choice of treatment for the patients. The antispasmodic drugs will be beneficial to both of the patient and the doctor.

A validated micro-sensitive stability-indicating adsorptive stripping voltammetric determination of Alverine citrate utilizing G

A validated micro-sensitive stability-indicating adsorptive stripping voltammetric determination of Alverine citrate utilizing G

Structural polymorphism research of alverine citrate

The study compares the active substance alverine citrate from three commercial sources in order to demonstrate polymorphic forms using the XRPD, SEM, and ATR-FTIR techniques. Based on the solubility tests of alverine citrate, a hard capsule was prepared with the highest possible dose of the active substance. The release profiles of alverine citrate and its stability were also investigated. XRPD and ATR-FTIR analysis shows that all alverine citrate samples (despite differences in the synthesis process) are in the same polymorphic Form I. Scanning electron micrographs of alverine citrate from each manufacturer show differences in morphology (texture). The solubility studies confirmed the complete solubility of the highest dose of alverine citrate in media with a pH of 1.2-6.8. The release studies show that the release of the active substance, regardless of the manufacturer type, meets the immediate release requirement. Accelerated stability studies confirm the stability of the alverine citrate from selected manufacturers. As a result, the manufacturer of the final medicinal product may allow their inter-changeability during production without compromising the safety or efficacy of the medicinal product.

The effect of alverine citrate plus simethicone (Meteospazmyl ) on effectiveness and tolerability of bowel preparation for colonoscopy

The effect of alverine citrate plus simethicone (Meteospazmyl ) on effectiveness and tolerability of bowel preparation for colonoscopy

Exploring 2:1 inclusion complexes of cyclodextrins and antispasmodics, Alverine citrate for enhancing bioavailability and sustained dischargement

Solubility development of supramolecular host–guest interaction between Alverine citrate with α and β-cyclodextrins were studied throughout the article. 2:1 host to guest stoichiometry of the inclusion complexation in the solution phase were confirmed by the Job’s plot. The IR, DSC, SEM and PXRD data turn out to be supportive about the phenomenon, inclusion complexation. Association constants and thermodynamic parameters of the inclusion complexes were obtained using UV–vis and spectrofluorometric measurement. The mechanism of inclusion complexation was explored by 1H and 2D ROESY NMR spectroscopy. Binding ability of the drug molecule, Alverine citrate with the HSA and the controlled release of the drug molecule from inclusion complexes were studied at PH-7.4 by spectrofluorimetricaly. Studied phenomenon thus develops the solubility of merely soluble drug into water, consequently makes bioavailable and enriches the drug delivery system.

The 5-HT and PLC Signaling Pathways Regulate the Secretion of IL-1β, TNF-α and BDNF from NG2 Cells

The present study was clarified the relationship between NG2 glial cells and 5-hydroxytryptamine (5-HT) to further revealed a role in the regulation of cortical excitability. The co-localization of NG2 cells and 5-HT in rat prefrontal cortex was determined using immunofluorescence. Different concentrations of 5-HT were applied to cultured NG2 cells. Real-time PCR measured the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and brain-derived neurotrophic factor (BDNF). Changes in the expression of IL-1β, TNF-α, and BDNF in NG2 cells were detected after the addition of 5-HT receptor specific blockers and phospholipase C (PLC) specific activators and inhibitors. The results confirmed that the NG2 protein and 5-HT co-localized in the prefrontal cortex. 5-HT treatment of NG2 cells significantly reduced the expression of IL-1β and BDNF mRNA and increased the expression of TNF-α. The 5-HT receptor specific inhibitors alverine citrate, ketanserin, ondansetron and SB-399885 blocked the regulatory effects of 5-HT on NG2 cells. The PLC signal was linked to the secretion of IL-1β, TNF-α and BDNF in NG2 cells. These results indicated that 5-HT affected IL-1β, TNF-α, and BDNF secretion from NG2 cells via the 5-HT1A, 5-HT2A, 5-HT3, 5-HT6 receptors and the PLC signaling pathway.

Alverine citrate promotes myogenic differentiation and ameliorates muscle atrophy

Sarcopenia is the age-related loss of muscle mass and function and no pharmacological medication has been approved for its treatment. We established an atrogin-1/MAFbx promoter assay to find drug candidates that inhibit myotube atrophy. Alverine citrate (AC) was identified using high-throughput screening of an existing drug library. AC is an established medicine for stomach and intestinal spasms. AC treatment increased myotube diameter and inhibited atrophy signals induced by either C26-conditioned medium or dexamethasone in cultured C2C12 myoblasts. AC also enhanced myoblast fusion through the upregulation of fusion-related genes during C2C12 myoblast differentiation. Oral administration of AC improves muscle mass and physical performance in aged mice, as well as hindlimb-disused mice. Taken together, our data suggest that AC may be a novel therapeutic candidate for improving muscle weakness, including sarcopenia.

Single Dose Study Assessing the Pharmacokinetic and Metabolic Profile of Alverine Citrate in Healthy Volunteers.

Alverine citrate is a spasmolytic commonly prescribed in conditions such as irritable bowel syndrome, painful diverticular disease of the colon, and primary dysmenorrhea. While clinical efficacy data on alverine alone or in combination with simethicone is freely available, surprisingly little information regarding the pharmacokinetics and metabolism of alverine can be found in literature. The first HPLC-MS/MS analytical protocol for determination of alverine parent, 4-hydroxy alverine, N-desethyl alverine and 4-hydroxy alverine glucuronide in human plasma was developed and validated. The two validated methods were used for analyzing plasma samples collected during an open label, non-comparative, single dose, one-period, one-treatment, pharmacokinetic and metabolic profile study of Spasmonal® Forte 120 mg hard capsule, conducted in 12 fasting healthy male and female volunteers of Caucasian descent. The study confirmed previous suspicions that parent alverine is subject to high pharmacokinetic variability and also revealed that the metabolic process most susceptible to outlying performance in Caucasians is hydroxylation to the active metabolite 4-hydroxy alverine. Another interesting observation made is that alverine parent accounts for only 3%, whereas total 4-hydroxy alverine (free and conjugated) accounts for 94% of alverine-related moieties in circulation (based on comparisons of total exposure).

Novel potentiometric methods for the estimation of bisoprolol and alverine in pharmaceutical forms and human serum

AbstractTwo new potentiometric sensors were created for the quantification of bisoprolol fumarate and alverine citrate in bulk pharmaceutical dosage forms and human serum. Bisoprolol and alverine sensors were manufactured by combining potassium tetrakis (p-chlorophenyl) borate ion pairs to serve as electroactive substances, plasticized poly (vinyl chloride) matrix membranes, ando-nitrophenyl octyl ether. They demonstrated high responses over the concentration ranges of 1.0×10−6to 1.0×10−2mol L−1bisoprolol and alverine with close to Nernstian cationic slopes of 52 and 56 mV decade−1, respectively. The detection limits for bisoprolol and alverine were 2.6×10−6and 1.75×10−6mol L−1, respectively. For both medications, the response time was instantaneous (2.0 s). The working pH ranges for bisoprolol and alverine were 4.50–8.50 and 2.00–8.80, respectively. For both sensors, the life cycle was long (3 months). The sensors were used in pharmaceutical dosage types for the assay of bisoprolol and alverine, recording average recoveries of 99.40% and 99.98% respectively and were also successfully used for estimating the two drugs in human serum with an average recovery of 99.60% for both drugs. For all multiple staged interfering materials, the reported latest potentiometric sensor methods displayed high selectivity. The current sensor obtained a high percentage recovery and an excellent relative standard deviation compared with those obtained from previously published methods.

Rectal Suppository of Mucoadhesive Microspheres of Alverine Citrate for İrritable Bowel Disease: In vitro Evaluation

The aim of present investigation was to develop chitosan based mucoadhesive microspheres of alverine citrate (ALV) for rectal delivery. Mucoadhesive microspheres of alverine citrate were prepared by simple emulsification crosslinking technique and evaluated for surface morphology, particle size, equilibrium swelling degree, drug content, in vitro bioadhesion and in vitro drug release. The suppositories of optimized batch of microspheres (AM5) were prepared by fusion method using cocoa butter, polyethylene glycol (PEG) 2000, PEG 4000 alone or in combinations with different ratios and evaluated for weight variation, hardness, drug content uniformity, liquefaction time, micro-melting range, in vitrodissolution and compatibility study by Attenuated total reflectance- Fourier transform infrared spectroscopy (ATR-FTIR). Chitosan based mucoadhesive microspheres of all batches of ALV except AM3 and AM4 showed spherical shape and particle size in the range of 76.56 to 294.32µm. All the formulations showed drug encapsulation efficiency in the range of 43.91 to 98.36% and bioadhesion in the range of 58.25 to 82.65%. AM5 batch showed 94.65% drug release at the end of 10h. Formulations of solid suppositories showed all the physical parameters within prescribed pharmacopoeial standard limits. Drug content of all the batches of suppositories was found to be in the range of 70.94 to 91.65%. All the batches of suppositories retarded the release of drug at the end of 10h. Suppository batch E showed 86.33% drug release at the end of 10h. Developed rectal formulation of ALV could be able to relieve the symptoms of irritable bowel disease and may overcome the disadvantages of oral delivery.

Meteospasmyl – a fixed combination of alverine citrate and simethicone in the treatment of digestive tract functional disorders

Meteospasmyl – a fixed combination of alverine citrate and simethicone in the treatment of digestive tract functional disorders

Abdominal pain. What the family doctors needs to know

The article is devoted to the problem of abdominal pain in the practice of family doctors. The main factors, mechanisms of occurrence, clinical manifestations and algorithm of diagnostics and treatment tactics are considered. The mechanisms of the appearance of smooth muscle’s spasm in the gastrointestinal tract and the role of various factors and, in particular, serotonin are described in details. The advantages and disadvantages of different myotropic spasmolytics are considered. The advantages of the selective blocker of serotonin 5-HT1a receptors – alverine citrate – in the treatment of smooth muscle’s spasm in the intestine are presented. It was carried out an analysis of the results of using alverine citrate/simethicone combination in both cases: in hypertonic and hyperkinetic dyskinesia of the upper gastrointestinal tract (including biliary ducts and sphincter of Oddi) and in hypertonic and hyperkinetic dyskinesia of the lower parts of the gastrointestinal tract.

An improved LC-MS/MS method for the quantification of alverine and para hydroxy alverine in human plasma for a bioequivalence study☆

A highly sensitive and selective high performance liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of alverine (ALV) and its active metabolite, para hydroxy alverine (PHA), in human plasma. For sample preparation, solid phase extraction of analytes was performed on Phenomenex Strata-X cartridges using alverine-d5 as the internal standard. The analytes were separated on Symmetry Shield RP18 (150mm×3.9mm, 5µm) column with a mobile phase consisting of acetonitrile and 10mM ammonium formate (65:35, v/v). Detection and quantitation was done by electrospray ionization mass spectrometry in the positive mode using multiple reaction monitoring. The assay method was fully validated over the concentration range of 15.0–15,000pg/mL for ALV and 30.0–15,000pg/mL for PHA. The intra-day and inter-day accuracy and precision (% CV) ranged from 94.00% to 96.00% and 0.48% to 4.15% for both the analytes. The mean recovery obtained for ALV and PHA was 80.59% and 81.26%, respectively. Matrix effect, expressed as IS-normalized matrix factor ranged from 0.982 to 1.009 for both the analytes. The application of the method was demonstrated for the specific analysis of ALV and PHA for a bioequivalence study in 52 healthy subjects using 120mg ALV capsules. The assay reproducibility was also verified by reanalysis of 175 incurred subject samples.

Method Development for Quantification of Loratidine and Alverine Citrate by Visible Spectrophotometry

The present work describes on two colorimetric methods based on charge transfer complex reaction of loratidine (LRT) and alverine citrate (ALV) with chloranilic acid in chloroform. The methods were developed on Perkin Elmer LAMBDA 25 UV –VIS spectrophotometer with 1cm quartz cells. The methods were optimised to achieve maximum colour intensity and validated for reliability. The coloured complexes showed maximum absorbance at 538 nm for LRT and 540 nm for ALV. The absorbances were found to increase linearly with increase in concentration which was emphasised by the calculated regression coefficients (0.9998-0.9999). Linearity of standard plot was in the order of 100-700 and 80-560µg/ml for LRT and ALV, respectively. The molar absorptivity, sandells sensitivity, LOD, LOQ and other validation parameters have been assessed extensively and all the parameters seem to comply with the acceptance criteria. The proposed methods were proved to be more accurate, simple, precise and rapid by statistical validation, recovery studies and could be appropriate to employ in regular laboratory analysis.

Novel Polymeric Membrane and Coated Wire Electrodes for Determination of Alverine Citrate in Pharmaceutical Formulations and Biological Fluids

Novel Polymeric Membrane and Coated Wire Electrodes for Determination of Alverine Citrate in Pharmaceutical Formulations and Biological Fluids

Pharmacologic Agents for Chronic Diarrhea.

Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly.

Method Development for Quantification of Donor-Acceptor Complexes of Alverine Citrate and Tapentadol by Visible Spectrophotometry

In this present work two colorimetric methods were developed based on donor-acceptor complexes of alverine citrate (ALV) and tapentadol (TAP) with cobalt thiocyanate. These methods were developed on Perkin Elmer LAMBDA 25 UV–VIS spectrophotometer with 1cm quartz cells. The colored species formed are the coordination complexes of the drugs (electron donor) and the central metal atom of cobalt thiocyanate (electron acceptor) which is extractable into nitrobenzene from aqueous solution. The reaction conditions were optimized and validated to achieve maximum colour intensity. The colored complexes show maximum absorbance measured at 625 nm for both ALV and TAP. The absorbances were found to increase linearly with an increase in concentration which was corroborated by the calculated regression coefficients (0.9998-0.9999). Linearity was obeyed in the range of 100-600 µg/ml for both ALV and TAP, respectively. The molar absorptivity, sandell’s sensitivity, LOD, LOQ and other validation parameters have been evaluated extensively as per ICH guidelines and all the parameters were found within the acceptance criteria for both methods. The proposed methods were proven to be more accurate, simple, precise and rapid by statistical validation of recovery studies and could be suitable for regular analysis.

Anxiolytic-like effects of alverine citrate in experimental mouse models of anxiety

Anxiety disorders are widely spread psychiatric illnesses that are a cause of major concern. Despite a consistent increase in anxiolytics, the prevalence of anxiety is static; this necessitates the development of new compounds with potential activity and minimum unwanted effects. A serotonergic (5HT) system plays an important role in pathogenesis of anxiety and predominantly involves 5HT1A receptor action in mediating anxiety-like behavior; the antagonism of 5HT1A receptor has demonstrated to produce anxiolytic-like effects. Alverine citrate (AVC) is reported as a 5HT1A antagonist; however, its effects on anxiety-like behavior are not investigated. Thus, the present study, by utilizing a neurobehavioral approach, examined the anxiolytic-like effects of AVC in experimental mouse models of anxiety.Mice were acutely treated with AVC (5–20mg/kg, i.p.)/diazepam (DIA, 2mg/kg, i.p.) and subjected to four validated anxiety models viz. elevated plus-maze (EPM), light/dark (L/D), hole-board (HB) and marble burying (MB) tests.AVC (15–20mg/kg) and DIA significantly increased open arm activity in EPM, exploration in light chamber in L/D test, exploratory behavior in HB and reduced MB behavior in marble burying test. AVC (5mg/kg) had no effect on all behavioral tests, while AVC (10mg/kg) produced partial effects. It revealed anxiolytic-like effects of AVC. Furthermore, anxiolytic-like effects of AVC at higher doses (15–20mg/kg) were more pronounced than lower doses (10mg/kg) and were quite similar to the standard drug DIA.The present finding demonstrates, for the first time, the anxiolytic-like effects of AVC, which may be an alternative approach for management of anxiety-related disorders.

Routine clinical administration of 4-week alverine citrate and simeticone combination relief global IBS symptoms

Introduction: The primary treatment aim for irritable bowel syndrome (IBS) is to relieve overall symptoms which can significantly impair the patient’s quality of life (QOL); however, it generally requires a high pill burden that may be improved by administration of combinatorial formulations. Thus, the effectiveness of alverine citrate and simeticone combination (ACS) for global symptom relief for IBS was investigated in this non-interventional study. Patients and Methods: ROME III IBS patients (n = 640; 52.3% male: mean age: 43.6 ± 12.5 years) with abdominal pain and discomfort ≥60 of 0-100 visual analogue scale (VAS) were included in a prospective, multicenter, non-interventional study at 26 Chinese sites from December 2010 to January 2012. Patients received alverine citrate (60 mg) with simeticone (300 mg) (ACS) 3× daily for 4 weeks. Pain/discomfort and bloating/distension were assessed by VAS. Global symptoms and QOL were assessed by 7-point and 5-point Likert scales, respectively. Post-treatment bowel function was assessed by Bristol Stool Form Scale (BSFS) and treatment-related adverse events (AEs) were recorded. Results: Of 640 patients, 540 (84.4%) completed the study, and 100 (15.6%) withdrew. In total, 87.5% reported bloating at baseline. After 4-week ACS treatment, 89.1% reported global symptom improvement. Furthermore, 4-week ACS treatment reduced pain and bloated VAS scores significantly from 78.4 ± 9.9 to 32.1 ± 21.0 and from 63.2 ± 27.2 to 22.6 ± 20.9, respectively (both p

Role of antispasmodics in the treatment of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT1A receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.