Mivacurium chloride CAS 106861-44-3
Introduction：Basic information about Mivacurium chloride CAS 106861-44-3, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Mivacurium chloride Basic information
| Product Name: | Mivacurium chloride |
| Synonyms: | MIVACURIUM CHLORIDE;rac Mivacurium Chloride;rac-BW-B 1090;rac-Mivacron;rel-(1R,1'R)-2,2'-[[(4E)-1,8-Dioxo-4-octene-1,8-diyl]bis(oxy-3,1-propanediyl)]bis[1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-1-[(3,4,5-trimethoxyphenyl)methyl]- isoquinolinium Chloride;[R-[R*,R*-(E)]]2,2'-(1,8-Dioxo-4-octene-1,8-diyl)bis(oxy-3,1-propanediyl)bis[1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxyphenyl)isoquinolinium] dichloride;rac-BW-B 1090U;-1，2，3，4-Te．trahydro-2-(3-hydroxypropyl)-6，7-dimethoxy-2-methyl-1-(3，4，5-trimethoxy-benzyl)isoquinolinium chloride，(E)-4-octenedioate(2：1) |
| CAS: | 106861-44-3 |
| MF: | C58H80ClN2O14+ |
| MW: | 1064.73 |
| EINECS: | 643-006-4 |
| Product Categories: | Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals;API |
| Mol File: | 106861-44-3.mol |
Mivacurium chloride Chemical Properties
| alpha | 20D -62.7° (c = 1.9 in water) |
| storage temp. | Hygroscopic, -20°C Freezer, Under Inert Atmosphere |
| solubility | DMSO: Soluble; Water: Soluble |
| form | A solid |
| color | White to off-white |
| Stability: | Hygroscopic |
| InChIKey | KFWHZSUNFAPZPW-NVIAPQDINA-M |
Safety Information
| Description | Mivacurium chloride,a mixture of three stereoisomers, is an intravenouslyadministered, short-acting skeletal muscle relaxant introduced as an adjunct to generalanesthesia. Structurally mivacurium chloride is closely related to doxacurium chlorideintroduced in 1991 by Wellcome as a muscle relaxant. It is a nondepolarizingneuromuscular blocking agent reportedly with a shorter duration of action and a morerapid rate of spontaneous recovery than other nondepolarizing agents. In extensiveclinical trials mivacurium chloride was well tolerated with few side effects. |
| Description | Mivacurium is an antagonist of nicotinic acetylcholine receptors (nAChRs) and muscarinic M2 and M3 receptors (ED50s = 0.08, 0.3, and 0.1 mg/kg for ex vivo human skeletal muscle nAChRs, guinea pig cardiac M2 receptors, and guinea pig bronchial M3 receptors, respectively). It inhibits acetylcholine-induced activation of neuronal nAChRs (IC50s = 69.04, 3.71, 1.52, and 2.90 for human α3β2-, α3β4-, α4β2-, and α7-containing nAChRs expressed in Xenopus oocytes). Mivacurium also inhibits adult human muscular α1β1εδ-containing nAChRs (IC50 = 3.69 nM in Xenopus oocytes expressing the human recombinant receptor). In vivo, mivacurium inhibits bradycardia and bronchoconstriction induced by vagal stimulation or acetylcholine in guinea pigs. It also induces neuromuscular blockade (ED95 = 80 μg/kg) in sheep with a more rapid onset time than atracurium and vecuronium . Formulations containing mivacurium have been used for pediatric anesthesia. |
| Chemical Properties | Off-White Solid |
| Originator | Wellcome (United Kingdom) |
| Uses | Non-depolarizing neuromuscular blocking agent. Muscle relaxant (skeletal) |
| Definition | ChEBI: Mivacurium chloride is a member of isoquinolines. |
| Manufacturing Process | To ()-5'-methoxylaudanosine (46.4 g) in methanol (240 mL) was added (-)-dibenzoyltartaric acid monohydrate (45.2 g). The mixture was heated toboiling, cooled at 5°C for 16 h and the (S)-(-)-5'-methoxylaudanosiniumdibenzoyltartrate salt (35.6 g, 80%) was filtered and discarded. The motherliquors were made basic with concentrated aqueous NaOH and evaporatedunder vacuum. The solid residue was partitioned between H2O and diethylether. The ether phase was dried and evaporated to an oil (24.9 g). To the oilin methanol (128 mL) was added (+)-dibenzoyltartaric acid monohydrate(26.6 g). The mixture was heated to boiling and cooled at 5°C for 16 h.Crystals were collected and recrystallized from methanol until a constantspecific rotation of [α]D20=+17.7° (1% EtOH) had been achieved. The yield of(R)-(+)-5'-methoxylaudanosinium dibenzoyltartrate as white crystals was 29.4g (66%). A portion of the salt (15.0 g) in methanol (200 mL) was made basicwith concentrated aqueous NaOH. The mixture was evaporated under vacuumand the residue was partitioned between H2O and diethyl ether. The combinedether layers were dried and evaporated under vacuum to yield 7.2 g (92%) of(R)-(-)-5'-methoxylaudanosine as an oil. (R)-(-)-5'-Methoxylaudanosine (7.2 g), 3-chloropropanol (3.5 g), sodiumiodide (5.6 g) and sodium carbonate (0.5 g) were refluxed in 2-butanone (125mL) for 16 h. The white suspension was filtered hot and solvent removed fromthe filtrate under vacuum. The residual gum was trituated with hot ethylacetate to remove excess 3-iodopropanol, dissolved in 200 mL methanol andpassed through a column packed with Dowex RTM.1-X8 ion exchange resin(60 g chloride form). The eluant was stripped of solvent under vacuum to giveN-3-hydroxypropyl-1-(R)-5'-methoxylaudanosinium chloride (8.4 g) as anamophous solid. The material was assayed by HPLC as a 2.3/1 mixture of the trans/cis diastereomers. N-3-Hydroxypropyl-1-(R)-5'-methoxylaudanosinium chloride (2.3/1, trans/cisby HPLC, 2.5 g) was dissolved in 60 mL 1,2-dichloroethane at about 70°C.(E)-4-Octene-1,8-dioic acid chloride (0.5 g) (K. Sisido, K. Sei, and H. Nozaki,J. Org. Chem., 1962, 27, 2681) was added and the mixture was stirred atambient temperature for 19 h. Solvent was removed under vacuum to give anamorphous solid which was dissolved in chloroform (25 mL) and washed with5% aqueous sodium chloride solution to remove unreacted quaternary salts.The chloroform layer was dried and evaporated under vacuum to give anamorphous solid. The acid ester impurities were substantially removed bywashing with hot 2-butanone. Residual solvent was evaporated under vacuumand the resulting amorphous solid was dissolved in methanol, filtered andlyophilized to give 1.9 g of (E)-(1R,1'R)-2,2'-[4-octenedioylbis(oxytrimethylene)]bis[1,2,4,3-tetrahydro-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxybenzyl)isoquinolinium] dichloride, which was assayed by HPLC as44.6% RS-RS (trans-trans) diester, 42.4% RR-RS (cis-trans) diester, 7.5% RRRR(cis-cis) diester, 4.0% RS (trans) acid ester and 1.5% RR (cis) (E)-(1R,1'R)-2,2'-[4-Octenedioylbis(oxytrimethylene)]bis[1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxybenzyl)isoquinolinium]dichloride acidester, [α]D20=-62.7° (1.9% in water). |
| Brand name | Mivacron (Abbott). |
| Therapeutic Function | Muscle relaxant |
| Biological Functions | Mivacurium chloride (Mivacron) is a newer agentthat is chemically related to atracurium. The primarymechanism of inactivation is hydrolysis by plasmacholinesterase. Although it is useful for patients withrenal or hepatic disease, some caution is warranted,since these individuals may have reduced plasmacholinesterase as a result of the disease.Mivacurium hasan onset of action (1.8 minutes) and duration of effect(20 minutes) only twice that of succinylcholine, and inthis respect, it is the most similar to succinylcholine ofall of the nondepolarizing agents. |
| General Description | Mivacurium chloride, 1,2,3,4-tetrahydro-2-(3-hydroxypropyl)-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxybenzyl)isoquinolinium chloride, (E)-4-octandioate (Mivacron), is a mixture of three stereoisomers,the trans-trans, cis-trans, and cis-cis diesters, each ofwhich has neuromuscular blocking properties. The cis-cisisomer is about one tenth as potent as the other isomers.Mivacurium chloride is a short-acting nondepolarizing drugused as an adjunct to anesthesia to relax skeletal muscle.The drug is hydrolyzed by plasma esterases, and it is likelythat anticholinesterase agents used as antidotes could prolongrather than reverse the effects of the drug. |
| References | [1] O A OKANLAMI C H A D Fryer. Interaction of nondepolarizing muscle relaxants with M2 and M3 muscarinic receptors in guinea pig lung and heart.[J]. Anesthesiology, 1996, 84 1: 155-161. DOI: 10.1097/00000542-199601000-00018 [2] MALIN JONSSON. Distinct pharmacologic properties of neuromuscular blocking agents on human neuronal nicotinic acetylcholine receptors: a possible explanation for the train-of-four fade.[J]. Anesthesiology, 2006, 105 3: 521-533. DOI: 10.1097/00000542-200609000-00016 [3] R.E. CLUTTON M. A G. A comparison of the neuromuscular and cardiovascular effects of vecuronium, atracurium and mivacurium in sheep[J]. Research in veterinary science, 1998, 64 3: Pages 233-237. DOI: 10.1016/s0034-5288(98)90131-x [4] RUIFENG ZENG. The efficacy and safety of mivacurium in pediatric patients.[J]. BMC Anesthesiology, 2017, 17 1: 58. DOI: 10.1186/s12871-017-0350-2 |
Mivacurium chloride Preparation Products And Raw materials
| Raw materials | 2-Butanone-->CHLOROETHANE-->3-Chloro-1-propanol-->PAPAVERINE-->Sodium carbonate-->L(+)-Tartaric acid-->DIBENZOATE-->Sodium iodide-->MELIBIOSE |
