Delving into the Latest Updates on Tolperisone Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Agileo, Instant release (IR) tolperisone tablets - Sanochemia, Sustained release tolperisone tablets - Sanochemia

+ [13]

Target

SCNA x VDCCs

Mechanism

SCNA blockers(Sodium channel alpha subunit blockers), VDCCs blockers(Voltage-gated calcium channel blockers)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesSkin and Musculoskeletal Diseases

Active Indication

Cardiovascular DiseasesMuscle Spasticity

Inactive Indication

Acute PainBack PainLordosis+ [6]

Originator Organization

Labatec Pharma SA

Active Organization

SANOCHEMIA Pharmazeutika GmbH

Labatec Pharma SA

Nanjing Baijingyu Pharmaceutical Co. Ltd.

Inactive Organization

Neurana Pharmaceuticals, Inc.

Avigen, Inc.

Drug Highest PhaseApproved

First Approval Date

CH (24 Aug 1966),

Muscle Spasticity

Regulation-

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Structure

Molecular FormulaC16H24ClNO

InChIKeyZBUVYROEHQQAKL-UHFFFAOYSA-N

CAS Registry3644-61-9

Tolperisone is a centrally acting muscle relaxant that has been used for the treatment of post-stroke spasticity and low back pain. Recently, the safety of tolperisone pharmaceutical products has been reassessed due to growing concerns over allergic adverse events. Reactive degradants of tolperisone may be responsible for these hypersensitivity reactions. By forming adducts with proteins, they may act as haptens that could evoke allergic reactions. The objective of this study was to examine the presence of these degradants in tolperisone pharmaceutical products and to assess their reactivity to elucidate their possible role in the pro-allergic effect of tolperisone. For this purpose, capillary electrophoresis UV detection (CE-UV) method was developed and validated for the quantification of degradants. A dual cyclodextrin system was applied to achieve the appropriate migration order enabling the analysis of 2-methyl-1-(4-methylphenyl)prop-2-en-1-one (MMP) and 1-(4-methylphenyl)propan-1-one (MMPO) in the presence of high concentrations of tolperisone. MMP was identified as the main degradant in forced degradation tests of the active pharmaceutical ingredient. Differences in MMP content of tolperisone products by different manufacturers have also been found, highlighting the role of formulation in their stability. High reactivity of MMP was demonstrated as rapid and almost complete adduct formation with cysteine was found. This degradant thus might be responsible for the allergic adverse effects of tolperisone even when it is present in trace amounts in tablets by readily reacting with proteins in vivo.

01 May 2024·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Tolperisone hydrochloride improves motor functions in Parkinson’s disease via MMP-9 inhibition and by downregulating p38 MAPK and ERK1/2 signaling cascade

Article

Author: Mostafa, Irona ; Bosu, Tory ; Esha, Nusrat Jahan Ikbal ; Chowdhury, Humayra Noor ; Sharmin, Ayesha ; Uddin, Kabir M ; Rahman, Mahbubur ; Hassan, Tazree ; Mallick, Anup ; Zaman, Bushra ; Islam, Mm Shanjid ; Chowdhury, Fowzia Afsana ; Ahmed, Shamim ; Hossain, Md Mainul

The mitogen-activated protein kinase (MAPK) signaling pathway, particularly the p38 MAPK and ERK1/2, has been implicated in the pathogenesis of Parkinson's disease (PD). Recent studies have shown that MAPK signaling pathway can influence the expression of matrix metalloproteinase 9 (MMP-9), known for its involvement in various physiological and pathological processes, including neurodegenerative diseases. This study explores the modulation of MMP-9 expression via the MAPK/ERK signaling cascade and its potential therapeutic implications in the context of PD-associated motor dysfunction. Here, tolperisone hydrochloride (TL), a muscle relaxant that blocks voltage-gated sodium and calcium channels, was used as a treatment to observe its effect on MAPK signaling and MMP-9 expression. Rotenone (RT) exposure in mice resulted in a significant reduction in substantia nigra and primary motor cortex neurons, which were further evidenced by impairments in motor function. When TL was administered, neuron count was restored (89.0 ± 4.78 vs 117.0 ± 4.46/mm²), and most of the motor dysfunction was alleviated. Mechanistically, TL reduced the protein expression of phospho-p38MAPK (1.06 fold vs 1.00 fold) and phospho-ERK1/2 (1.16 fold vs 1.02 fold), leading to the inhibition of MAPK signaling, as well as reduced MMP-9 concentrations (2.76 ± 0.10 vs 1.94 ± 0.10 ng/mL) in the process of rescuing RT-induced neuronal cell death and motor dysfunction. Computational analysis further revealed TL's potential inhibitory properties against MMP-9 along with N and L-type calcium channels. These findings shed light on TL's neuroprotective effects via MMP-9 inhibition and MAPK signaling downregulation, offering potential therapeutic avenues for PD-associated motor dysfunction.

09 Apr 2024·Cureus Journal of Medical Science

Symptomatic Cavum Vergae Cyst in a Geriatric Patient: A Report of a Rare Case and Conservative Management Approach

Author: Petrov, Petar-Preslav ; Velev, Andrey ; Penchev, Plamen ; Velchev, Vladislav

Cavum vergae (CV) cysts constitute a small proportion of intracranial cysts, and although generally asymptomatic, there are occasional cases where they might exhibit clinical manifestations. We present a clinical case of a 79-year-old female patient who had a clinical manifestation of headache on the occipital side of the head with irradiation to the shoulder girdle as well as numbness, dizziness, visual impairment, sleep disturbances, and tingling in the hands for three months. Vertigo and rightward staggering had been experienced for two weeks. On physical examination, it was discovered that there was smoothed physiological lordosis, restricted and painful movements, and paravertebral muscle rigidity in the cervical region. The patient had bilaterally reduced biceps and triceps reflexes, painful Erb's points, and hypesthesia over the C5 and C6 dermatomes on the right side. The patient had decreased coordination and displayed staggered movement to the right. A CT scan discovered dilated subarachnoid spaces of the convexity and a CV cyst. The patient was prescribed conservative therapy consisting of etoricoxib oral at a dosage of 2 × 60 mg for seven days, tolperisone hydrochloride orally at a dosage of 2 × 150 mg for seven days, pregabalin 75 mg, one pill in the evening for seven days, ozoid (a gel containing ozone) for external application, and vinpocetine 2 × 10 mg orally for two months. Following the conservative treatment, the patient exhibited improvement in her symptoms and no longer had challenges carrying out her daily tasks. Furthermore, six months after the therapy, the patient did not experience any symptoms. Long-term follow-up will be conducted in cases of symptom recurrence or cyst enlargement.

2

News (Medical) associated with Tolperisone Hydrochloride

27 Mar 2023

·www.drugs.com

Comparative Effectiveness of Meds for Acute Low Back Pain Unclear

MONDAY, March 27, 2023 -- For patients with acute low back pain , the comparative effectiveness and safety of analgesic medications is unclear, according to a systematic review and meta-analysis published online March 22 in The BMJ . Michael A. Wewege, from the University of New South Wales in Sydney, and colleagues conducted a systematic review and network meta-analysis to assess the comparative effectiveness and safety of analgesic medicines for acute nonspecific low back pain. Data were reviewed from 98 randomized controlled trials (15,134 participants), which included 69 medicines and combinations. The researchers observed low or very low confidence in evidence for reduced pain intensity after treatment with tolperisone, aceclofenac plus tizanidine, pregabalin (mean differences, −26.1, −26.1, and −24.7, respectively), and 14 other medicines versus placebo. There was low or very low confidence seen for no difference between the effects of several of these medications. There was moderate to very low confidence noted for increased adverse events with tramadol, acetaminophen plus sustained-release tramadol, baclofen, and acetaminophen plus tramadol compared with placebo (risk ratio, 2.6, 2.4, 2.3, and 2.1, respectively). There was moderate-to-low confidence for these medicines increasing the risk for adverse events compared with other medicines. For secondary outcomes and a secondary analysis of medicine classes, moderate-to-low confidence was also noted. "Despite nearly 60 years of research involving more than 15,000 patients, high quality evidence to guide clinical decisions on analgesic medicines for acute nonspecific low back pain remains limited," the authors write. The Sydney Pharmacy School receives funding from GlaxoSmithKline for a postgraduate scholarship supporting a research student supervised by one of the authors. Abstract/Full Text Posted March 2023

Clinical Result

24 Nov 2021

·www.biospace.com

Neurana Pharmaceuticals to Present at Piper Sandler Healthcare Conference

SAN DIEGO, Nov. 24, 2021 /PRNewswire/ --Neurana Pharmaceuticals, Inc. a biotechnology company focused on the treatment of neuromuscular conditions, today announced that Craig Thompson, President and Chief Executive Officer, will present at the 33rd Annual Piper Sandler Healthcare Conference and participate in one-on-one meetings with investors. The conference takes place virtually November 29th – December 2nd. Presentations will be available for registered attendees via the Piper Sandler conference site. About Neurana Pharmaceuticals, Inc. Neurana Pharmaceuticals, Inc. is a privately held, clinical-stage, biotechnology company focused on the treatment of neuromuscular conditions, including acute, painful muscle spasms of the back. The company was founded in 2013 and is based in San Diego. Neurana's lead development compound is tolperisone, a novel, non-opioid, non-drowsy, non-cognitive impairing treatment, which the company is developing for the large population of patients who experience muscle spasms. For additional information, please visit .

100 Deals associated with Tolperisone Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D01507	Tolperisone Hydrochloride	M02AX06 M03BX04	DB06264

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Cardiovascular Diseases	CN	Nanjing Baijingyu Pharmaceutical Co. Ltd.	01 Jan 1986
Muscle Spasticity	CH	Labatec Pharma SA	24 Aug 1966

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Pain	Phase 3	US	Neurana Pharmaceuticals, Inc.	15 Dec 2020
Back Pain	Phase 3	US	Neurana Pharmaceuticals, Inc.	15 Dec 2020
Lordosis	Phase 3	US	Neurana Pharmaceuticals, Inc.	15 Dec 2020
Spasm	Phase 3	US	Neurana Pharmaceuticals, Inc.	15 Dec 2020
Low Back Pain	Phase 2	US	Neurana Pharmaceuticals, Inc.	01 Feb 2019
Muscle Cramp	Phase 2	US	Neurana Pharmaceuticals, Inc.	01 Feb 2019
Multiple Sclerosis	Phase 2	CZ	Avigen, Inc.	01 Sep 2007
Multiple Sclerosis	Phase 2	DE	Avigen, Inc.	01 Sep 2007
Multiple Sclerosis	Phase 2	RU	Avigen, Inc.	01 Sep 2007
Multiple Sclerosis	Phase 2	RS	Avigen, Inc.	01 Sep 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04671082 (RESUME-1, Biospace) Manual	Phase 3	Muscle Spasticity	1,004	Tolperisone Hydrochloride	dsibgskgyh(qmlvfucfeh) = failed to meet its primary endpoints kkyimbxwtx (iwzyxqmcxr )	Positive	22 Mar 2022
NCT03802565 (STAR, CTgov)	Phase 2	Low Back Pain \| Spasm \| Acute Pain ... View more	415	Tolperisone (Tolperisone 50 mg)	ngnssgpbgu(fkfvirbxnu) = pknkyhvzrz lsfmixizlr (tsiuudptgi, sykgslmfou - yuhgbogbxp) View more	-	10 Nov 2020
				Tolperisone (Tolperisone 100 mg)	ngnssgpbgu(fkfvirbxnu) = oprgjrilmj lsfmixizlr (tsiuudptgi, yyzgnnhjrv - qwfpvbiykp) View more
EULAR2003	Not Applicable	Acute low back pain	279	Tolperisone 150 mg tablets t.i.d.	msuldkmuop(fhtnzstbyu) = yyvltvakkq rxctxlqmbd (rxuziysptk )	Positive	18 Jun 2003
				Placebo	msuldkmuop(fhtnzstbyu) = nwzznxymgm rxctxlqmbd (rxuziysptk )