Delving into the Latest Updates on Mebeverine Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Mebeverine, Mebeverine hydrochloride (USAN)

+ [5]

Target

mAChRs

Action

antagonists

Mechanism

mAChRs antagonists(Muscarinic acetylcholine receptor antagonists)

Therapeutic Areas

Nervous System DiseasesDigestive System DisordersSkin and Musculoskeletal Diseases+ [1]

Active Indication

Abdominal PainDiarrheaFlatulence+ [3]

Inactive Indication-

Originator Organization-

Active Organization

Viatris Pty Ltd.

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date

Australia (28 Aug 2001),

Abdominal PainDiarrheaFlatulence+ [2]

Regulation-

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Structure/Sequence

Molecular FormulaC25H36ClNO5

InChIKeyPLGQWYOULXPJRE-UHFFFAOYSA-N

CAS Registry2753-45-9

View All Structures (2)

BACKGROUND & AIMSPediatric irritable bowel syndrome and functional abdominal pain-not otherwise specified lack effective pharmacologic interventions. The efficacy of mebeverine, an antispasmodic agent, and the effect of labeling within a pediatric cohort were evaluated.METHODSThis randomized trial was conducted across 13 hospitals. Participants (12-17 years) with irritable bowel syndrome or functional abdominal pain-not otherwise specified received mebeverine (200 mg twice daily) or placebo for 8 weeks. Treatment was labeled as "mebeverine or placebo" (blinded trial label) or "mebeverine" (mebeverine label), creating the following 4 groups: (1) mebeverine-blinded trial label, (2) mebeverine-mebeverine label, (3) placebo-blinded trial label, and (4) placebo-mebeverine label. Randomization (1:1:1:1) was masked to physicians, except for drug labeling. Primary end point was treatment success (>50% reduction of abdominal pain intensity and frequency) after 8 weeks. The key secondary end point was adequate relief of symptoms.RESULTSOf the 269 randomized patients, treatment success was similar between those receiving mebeverine (groups 1 and 2) (n = 31 [23.4%]) and placebo (groups 3 and 4) (n = 30 [22.0%]; odds ratio [OR], 1.08; 95% CI, 0.59-1.99; P = .81). Treatment success was higher in groups with the mebeverine label (groups 2 and 4) (n = 42 [31.6%]) compared with the blinded trial label (groups 1 and 3) (n = 19 [14.1%]; OR, 2.84; 95% CI, 1.52-5.34; P = .001). Adequate relief rates were similar between mebeverine (n = 55 [41.0%]) and placebo groups (n = 61 [45.5%]; OR, 0.83; 95% CI, 0.51-1.35; P = .46), but higher in Mebeverine-labeled groups (n = 67 [50.4%]) compared with blinded trial-labeled groups (n = 49 [36.3%]; OR, 1.78; 95% CI, 1.1-2.9; P = .02). Adverse events were mild and infrequent.CONCLUSIONSMebeverine was ineffective in treatment of pediatric irritable bowel syndrome and functional abdominal pain-not otherwise specified. However, a positive drug label significantly enhanced treatment outcomes compared with a blinded trial label. International Clinical Trials Registry Platform, Number: NL-OMON55563.

01 Sep 2024·eBioMedicine

Tanomastat exerts multi-targeted inhibitory effects on viral capsid dissociation and RNA replication in human enteroviruses

Article

Author: Jaladanki, Chaitanya K. ; Fan, Hao ; Wong, Yi Hao ; Jaladanki, Chaitanya K ; Yogarajah, Thinesshwary ; Chu, Justin Jang Hann ; Lim, Therese Yien May

BACKGROUNDGlobal cyclical outbreaks of human enterovirus infections has positioned human enterovirus A71 (EV-A71) as a neurotropic virus of clinical importance. However, there remains a scarcity of internationally approved antivirals and vaccines.METHODSIn pursuit of repurposing drugs for combating human enteroviruses, we employed a comprehensive pharmacophore- and molecular docking-based virtual screen targeting EV-A71 capsid protein VP1-4, 3C protease, and 3D polymerase proteins. Among 15 shortlisted ligand candidates, we dissected the inhibitory mechanism of Tanomastat in cell-based studies and evaluated its in vivo efficacy in an EV-A71-infected murine model.FINDINGSWe demonstrated that Tanomastat exerts dose-dependent inhibition on EV-A71 replication, with comparable efficacy profiles in enterovirus species A, B, C, and D in vitro. Time-course studies suggested that Tanomastat predominantly disrupts early process(es) of the EV-A71 replication cycle. Mechanistically, live virus particle tracking and docking predictions revealed that Tanomastat specifically impedes viral capsid dissociation, potentially via VP1 hydrophobic pocket binding. Bypassing its inhibition on entry stages, we utilized EV-A71 replication-competent, 3D^pol replication-defective, and bicistronic IRES reporter replicons to show that Tanomastat also inhibits viral RNA replication, but not viral IRES translation. We further showed that orally administered Tanomastat achieved 85% protective therapeutic effect and alleviated clinical symptoms in EV-A71-infected neonatal mice.INTERPRETATIONOur study establishes Tanomastat as a broad-spectrum anti-enterovirus candidate with promising pre-clinical efficacy, warranting further testing for potential therapeutic application.FUNDINGMOE Tier 2 grants (MOE-T2EP30221-0005, R571-000-068-592, R571-000-076-515, R571-000-074-733) and A∗STARBiomedical Research Council (BMRC).

01 Jul 2024·Journal of Applied Spectroscopy

Spectrophotometric Method Using the Derivative for the Determination of the Drug Losartan

Author: Hassan, Dheefaf F. ; Sadiq, Kawther Ahmed ; Mohammed, Maha A. ; Mezaal, Elham N.

A sensitive, easy, and low-cost method used in the determination of pure forms of losartan and mebeverine hydrochloride, also in pharmaceutical preparations with derivative spectrometry using UV-Vis technol.This method depends on measuring the first derivative of the spectrum using zero cross, peak to base line, and peak area.The linear range of concentrations used was equal to 2-14 ppm for losartan, whereas for mebeverine hydrochloride it was equal to 2-16 ppm in a mixtureFor losartan, in the presence of mebeverine hydrochloride, 12 ppm by utilizing peak to baseline correlation coefficients 0.9984, 0.9994, and peak area 0.9972, whereas for mebeverine hydrochloride in the presence of losartan, 12 ppm by utilizing peak to fundamental correlation coefficients 0.9952, 0.9966, 0.9957, and peak area 0.9970, 0.9971, 0.9968, 0.9971.The limit of detection for each drug, losartan and mebeverine hydrochloride, is equal to 0.0113 ppm.The accuracy and precision of the method were estimated by calculating relative standard deviation (%RSD) values less than 3% while maintaining a recovery percentage of acceptable value.The proposed method proved effective and efficient at estimating both losartan and mebeverine hydrochloride, in the presence of the other in a mixture of the two without interference, despite the closeness of their spectral absorption peaks.There are no other more accurate methods for estimating the two in a mixture than the proposed method.The proposed method is considered one of the most direct and economical methods that do not require reagents or addnl. materials for conducting reactions and studying the optimal conditions for those interactions.Thus, it is considered one of the green chem. techniques that reduce the use of chems. and reagents in the process of estimating these drugs in a mixture and in a shorter period of time.The proposed method can be used to estimate the different properties in a mixture of the two compounds whose absorption spectra are close.

100 Deals associated with Mebeverine Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D04868	Mebeverine Hydrochloride	A03AA04	DB12554

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Abdominal Pain	Australia	Viatris Pty Ltd.	28 Aug 2001
Diarrhea	Australia	Viatris Pty Ltd.	28 Aug 2001
Flatulence	Australia	Viatris Pty Ltd.	28 Aug 2001
Irritable Bowel Syndrome	Australia	Viatris Pty Ltd.	28 Aug 2001
Muscle Cramp	Australia	Viatris Pty Ltd.	28 Aug 2001
Gastrospasm	-	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05175131 (CTgov)	Phase 3	Abdominal Pain \| Irritable Bowel Syndrome	465	Simethicone+Mebeverine (Mebeverine+Simethicone Combination)	myybimoggz(yudyfvqbsy) = drltqvbipr qzplqyswyu (uurzscjkdj, lqueurmxoc - wrnejbtdxw) View more	-	03 Jan 2024
				Mebeverine (Mebeverine)	myybimoggz(yudyfvqbsy) = dlgvqrwxeg qzplqyswyu (uurzscjkdj, qpftqzuoul - vhvfcfsjgx) View more