関: tolperisone hydrochloride

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/29 16:41:31」(JST)

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Tolperisone, a piperidine derivative, is a centrally-acting muscle relaxant. Trade names include Biocalm, Muscodol, Mydeton, Mydocalm, Myolax, Myoxan and Viveo.

Clinical use

In Tolperisone is indicated for use in the treatment of pathologically increased tone of the cross-striated muscle caused by neurological diseases (damage of the pyramidal tract, multiple sclerosis, myelopathy, encephalomyelitis) and of spastic paralysis and other encephalopathies manifested with muscular dystonia.^[1]^[2]

Other possible uses include:^{[citation needed]}

Spondylosis
Spondylarthrosis
Cervical and lumbar syndromes
Arthrosis of the large joints
Obliterating atherosclerosis of the extremity vessels
Diabetic angiopathy
Thromboangiitis obliterans
Raynaud's syndrome

Contraindications and cautions

Manufacturers report that tolperisone should not be used in patients with myasthenia gravis. Only limited data are available regarding the safety in children, youths, during pregnancy and breastfeeding. It is not known whether tolperisone is excreted into mother's milk.^[1]^[2]

Side effects

Adverse effects occur in fewer than 1% of patients and include muscle weakness, headache, arterial hypotension, nausea, vomiting, dyspepsia, and dry mouth. All effects are reversible.^[1]^[2] Allergic reactions occur in fewer than 0.1% of patient and include skin rash, hives, Quincke's edema, and in some cases anaphylactic shock.^[1]^[3]

Overdose

Excitability has been noted after ingestion of high doses by children.^[1] In suicide studies of three isolated cases, it is believed that ingestion of tolperisone was the cause of death.^[4]

Interactions

Tolperisone does not have a significant potential for interactions with other pharmaceutical drugs. It cannot be excluded that combination with other centrally-acting muscle relaxants, benzodiazepines or non-steroidal anti-inflammatory drugs (NSAIDs) may make a dose reduction necessary in some patients.^[1]^[2]

Mechanism of action

Tolperisone is a centrally-acting muscle relaxant that acts at the reticular formation in the brain stem^[1] by blocking voltage-gated sodium and calcium channels.^[5]^[6]

Pharmacokinetics

Tolperisone is absorbed nearly completely from the gut and reaches its peak blood plasma concentration after 1.5 hours. It is extensively metabolised in the liver and kidneys. The substance is excreted via the kidneys in two phases; the first with a half-life of two hours, and the second with a half-life of 12 hours.^[1]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 5510–1. ISBN 978-3-85200-181-4.
^ ^a ^b ^c ^d "Midocalm". Romania: InfoMedic.
^ Ribi C, Vermeulen C, Hauser C (2003). "Anaphylactic reactions to tolperisone (Mydocalm)". Swiss Medical Weekly 133 (25–26): 369–371. PMID 12947534.
^ Sporkert, F.; Brunel, C.; Augsburger, M. P.; Mangin, P. (2012). "Fatal tolperisone poisoning: Autopsy and toxicology findings in three suicide cases". Forensic Science International 215 (1): 101–104. doi:10.1016/j.forsciint.2011.05.025. PMID 21683537.
^ Kocsis P, Farkas S, Fodor L, Bielik N, Thán M, Kolok S, Gere A, Csejtei M, Tarnawa I (2005). "Tolperisone-type drugs inhibit spinal reflexes via blockade of voltage-gated sodium and calcium channels". Journal of Pharmacology and Experimental Therapeutics 315 (3): 1237–1246. doi:10.1124/jpet.105.089805. PMID 16126840.
^ Hofer D, Lohberger B, Steinecker B, Schmidt K, Quasthoff S, Schreibmayer W (2006). "A comparative study of the action of tolperisone on seven different voltage dependent sodium channel isoforms". European Journal of Pharmacology 538 (1–3): 5–14. doi:10.1016/j.ejphar.2006.03.034. PMID 16650844.

External links

"Tolperisone: Administration & Dosage - Papers". Poland: BioInfo. ^{[dead link]}

UpToDate Contents

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1. 亜急性および慢性腰痛：薬物治療と非侵襲的治療 subacute and chronic low back pain pharmacologic and noninterventional treatment

English Journal

Enantiomeric separation of tolperisone and eperisone by reversed-phase HPLC with cellulose tris(3-chloro-4-methylphenylcarbamate)-coated chiral column.

Owada Y1, Takahashi M, Iwasa S, Ichiba H, Sadamoto K, Fukushima T.Author information 1Department of Clinical Science, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-shi, Chiba, 274-8510, Japan.AbstractEnantiomeric separations of centrally acting muscle relaxants, that is, tolperisone (TOL) and eperisone (EP), that are marketed as racemates were investigated by reversed-phase high-performance liquid chromatography (HPLC) on a polysaccharide-based chiral column. Both TOL and EP are basic drugs because they contain a tertiary amino group and have similar chemical structures with the exception of the p-methylphenyl and p-ethylphenyl groups in TOL and EP, respectively. A reversed-phase chiral column, that is, a Chiralcel OZ-RH column, which bears cellulose tris(3-chloro-4-methylphenylcarbamate) as the chiral moiety, was effective for the enantiomeric separation of TOL and EP enantiomers. The separation factor and resolution values obtained for TOL were 1.22 and 1.66, respectively, and those for EP were 1.21 and 2.24, respectively, using a 20 mm ammonium acetate in H2 O (pH 8.0 and 7.0, respectively)-CH3 CN (70:30) mobile phase. Using the proposed HPLC conditions, it was found that (R)-TOL eluted faster than (S)-TOL, as revealed by the optical rotation and circular dichroism spectroscopy. In contrast, EP was easily racemized under the experimental conditions, and hence, the elution order was not determined.
Biomedical chromatography : BMC.Biomed Chromatogr.2014 Jan;28(1):102-5. doi: 10.1002/bmc.2892. Epub 2013 Mar 15.
Enantiomeric separations of centrally acting muscle relaxants, that is, tolperisone (TOL) and eperisone (EP), that are marketed as racemates were investigated by reversed-phase high-performance liquid chromatography (HPLC) on a polysaccharide-based chiral column. Both TOL and EP are basic drugs beca
PMID 23505060

Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity guidelines.

Gold R1, Oreja-Guevara C.Author information 1Department of Neurology, St Josef-Hospital/Ruhr-University Bochum, Bochum, Germany.AbstractSymptomatic therapy of multiple sclerosis (MS) is an important part of a comprehensive treatment plan that aims to improve patients' quality of life. In the current era of medical progress, several factors have led to the development of guidelines for MS management. There is continued need for an evidence-based approach supported by high-quality data from controlled clinical trials. Most healthcare systems require this approach and include it in the reimbursement process. Guidelines are usually committed by national or continental neurological societies. The Spanish Society of Neurology demyelinating diseases working group has developed a consensus document on spasticity in patients with MS. MS experts from the group used the metaplan method to sum up the most important recommendations about spasticity for inclusion in the guidance. Recommendations were classified according to the Scottish Intercollegiate Guidelines Network system and approved by all members of the group. In Germany, the guideline panel of the German Neurological Society endorsed the national competence network for multiple sclerosis (Krankheitsbezogenes Kompetenznetz Multiple Sklerose) to update the existing recommendations. The most recent fifth edition of the guidelines (dated April 2012) now also includes recommendations for treatment of key symptoms such as spasticity. More than 30 MS neurologists contributed to the new edition reflecting the need for broad expertise. After a first round in which key topics were defined, a web-based decision process was undertaken to further develop individual topics such as symptomatic therapy. The draft manuscript was reviewed once again by the group prior to submission to the official review process. The aims of spasticity treatment are to improve mobility and dexterity, achieve physiological movement patterns, reduce pain, facilitate nursing measures and avoid complications such as contractures. Representative antispasticity medications include baclofen, tizanidine, gabapentin, dantrolene, tolperisone, benzodiazepines and Sativex® oromucosal spray. Botulinum toxin and intrathecal baclofen may also be required in selected cases. Plans are currently in motion to develop next-level European guidelines through a concerted approach coordinated by the European Federation of Neurological Societies.
Expert review of neurotherapeutics.Expert Rev Neurother.2013 Dec;13(12 Suppl):55-9. doi: 10.1586/14737175.2013.865880.
Symptomatic therapy of multiple sclerosis (MS) is an important part of a comprehensive treatment plan that aims to improve patients' quality of life. In the current era of medical progress, several factors have led to the development of guidelines for MS management. There is continued need for an ev
PMID 24289845

Chemometrics-Assisted UV Spectrophotometric and RP-HPLC Methods for the Simultaneous Determination of Tolperisone Hydrochloride and Diclofenac Sodium in their Combined Pharmaceutical Formulation.

Gohel NR, Patel BK, Parmar VK.Author information Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT Campus, Changa - 388 421, Ta. Petlad, Dist. Anand, Gujarat, India.AbstractChemometrics-assisted UV spectrophotometric and RP-HPLC methods are presented for the simultaneous determination of tolperisone hydrochloride (TOL) and diclofenac sodium (DIC) from their combined pharmaceutical dosage form. Chemometric methods are based on principal component regression and partial least-square regression models. Two sets of standard mixtures, calibration sets, and validation sets were prepared. Both models were optimized to quantify each drug in the mixture using the information included in the UV absorption spectra of the appropriate solution in the range 241-290 nm with the intervals λ = 1 nm at 50 wavelengths. The optimized models were successfully applied to the simultaneous determination of these drugs in synthetic mixture and pharmaceutical formulation. In addition, an HPLC method was developed using a reversed-phase C18 column at ambient temperature with a mobile phase consisting of methanol:acetonitrile:water (60:30:10 v/v/v), pH-adjusted to 3.0, with UV detection at 275 nm. The methods were validated in terms of linearity, accuracy, precision, sensitivity, specificity, and robustness in the range of 3-30 μg/mL for TOL and 1-10 μg/mL for DIC. The robustness of the HPLC method was tested using an experimental design approach. The developed HPLC method, and the PCR and PLS models were used to determine the amount of TOL and DIC in tablets. The data obtained from the PCR and PLS models were not significantly different from those obtained from the HPLC method at 95% confidence limit.
Scientia pharmaceutica.Sci Pharm.2013 Jul 14;81(4):983-1001. doi: 10.3797/scipharm.1306-01. eCollection 2013.
Chemometrics-assisted UV spectrophotometric and RP-HPLC methods are presented for the simultaneous determination of tolperisone hydrochloride (TOL) and diclofenac sodium (DIC) from their combined pharmaceutical dosage form. Chemometric methods are based on principal component regression and partial
PMID 24482768

Japanese Journal

Antinociceptive Effects of Sodium Channel-Blocking Agents on Acute Pain in Mice

Sakaue Akiko,Honda Motoko,Tanabe Mitsuo,Ono Hideki
Journal of Pharmacological Sciences 95(2), 181-188, 2004
… The drugs used were mexiletine, lidocaine, carbamazepine, phenytoin, eperisone, tolperisone, and zonisamide. … In the sciatic nerve isolated from mice, mexiletine, lidocaine, eperisone, and tolperisone impaired the propagation of low frequency action potentials (evoked at 0.2 Hz). …
NAID 130000074392

Method for Recording Spinal Reflexes in Mice: Effects of Thyrotropin-Releasing Hormone, DOI, Tolperisone and Baclofen on Monosynaptic Spinal Reflex Potentials

Okada Hiroki,Honda Motoko,Ono Hideki
The Japanese journal of pharmacology 86(1), 134-136, 2001-05-01
… Tolperisone hydrochloride and baclofen produced transient and long-lasting MSR depressions, respectively. …
NAID 10007121872

運動失調マウスの脊髄反射電位 : TRHアナログの作用と下行性ノルアドレナリン神経系の機能変化

小野秀樹,岡田啓希,本多基子
日本薬理学雑誌 : FOLIA PHARMACOLOGICA JAPONICA 116, 68P-72P, 2000-11-01
… Tolperisone and baclofen produced transient and long-lasting MSR depression, respectively. …
NAID 10013935430

「トルペリゾン」

Tolperisone
Systematic (IUPAC) name
	2-methyl-1-(4-methylphenyl)-3-(1-piperidyl)propan-1-one
Clinical data
Trade names	Mydocalm and others
AHFS/Drugs.com	International Drug Names
Legal status	℞ Prescription only
Routes	Oral, parenteral
Pharmacokinetic data
Metabolism	Liver, kidney
Half-life	1st phase: 2 hrs; 2nd phase: 12 hrs
Excretion	Renal
Identifiers
CAS number	728-88-1
ATC code	M02AX06 M03BX04
PubChem	CID 5511
UNII	F5EOM0LD8E
KEGG	D08617
ChEMBL	CHEMBL1076211
Chemical data
Formula	C16H23NO
Mol. mass	245.36 g/mol
	SMILES C1CCCN(C1)CC(C(C2=CC=C(C=C2)C)=O)C;
	InChI InChI=1S/C16H23NO/c1-13-6-8-15(9-7-13)16(18)14(2)12-17-10-4-3-5-11-17/h6-9,14H,3-5,10-12H2,1-2H3 ; Key:FSKFPVLPFLJRQB-UHFFFAOYSA-N ;
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