Mivacurium Chloride

Product Overview

Mivacurium Chloride is a benzylisoquinolinium non-depolarizing muscle relaxant: a symmetric bis-quaternary ammonium dichloride in which two 6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxybenzyl)tetrahydroisoquinolinium units are joined by a diester linking chain containing an (E)-oct-4-enedioyl group.

Mechanistic origin of “short-acting”: The two ester bonds in the molecule are rapidly hydrolyzed by plasma cholinesterase (butyrylcholinesterase) to metabolites without neuromuscular blocking activity. This is exactly why it is short-acting with fast recovery—and also the source of its most important clinical contraindication (see the end of this page).

Why it is a mixture: Mivacurium is a mixture of three stereoisomers—the trans-trans diester (1R,1’R,2S,2’S), the cis-trans diester (1R,1’R,2R,2’S), and the cis-cis diester (1R,1’R,2R,2’R)—in a ratio of approximately 60:35:6. The trans-trans and cis-trans isomers together account for 92%–96%; cat model studies show their neuromuscular blocking potencies are not significantly different from each other or from mivacurium overall, while the cis-cis isomer is about one-tenth as potent as the other two. Therefore, this mixture is regarded pharmaceutically as a single active substance, and quality control must control the ratio of all three isomers simultaneously.

Pharmacological profile: It competitively antagonizes nicotinic acetylcholine receptors at the motor endplate, blocking the action of acetylcholine to produce skeletal muscle relaxation; it does not cause depolarization or fasciculation. The ED95 (mean dose required to suppress the adductor pollicis twitch response to ulnar nerve stimulation by 95%) is approximately 0.07 mg/kg.

Technical Specifications

• Standards: CHP/USP/EP

• Specification: 0.99 (purity ≥99.0%, HPLC); the ChP formulation monograph and import registration standards require control against the labeled amount

• CAS Number: 106861-44-3 (EINECS; UNII 600ZG213C3; KEGG DRUG D00763; ChEBI 6959; PubChem CID 5281080)

• Molecular Formula: C₅₈H₈₀Cl₂N₂O₁₄

• Molecular Weight: 1100.17 (Selleck, US Biological, TCI record 1100.18); ChP and various labels record 1100.18; exact mass 1098.500

• Appearance: Off-white to yellow amorphous solid (HCSC product monograph); some suppliers describe it as a white to pale yellow solid or white crystalline powder

• Purity (HPLC): ≥ 99.0%

• Melting Point: Decomposes at about 125 ℃ (Canadian MIVACRON product monograph; recommended). Suppliers additionally record 96 ℃ (decomposition) and >96 ℃ (decomposition)—sources differ considerably and all describe “decomposition” rather than true melting; when citing, state the source and measurement method; an amorphous solid itself has no definite crystalline melting point

• Specific Rotation: [α]D²⁰ −62.7° (C=1.9, water); other sources record −63° to −56° (c=1.9, H₂O). Note: this product is a mixture of three stereoisomers; specific rotation varies with isomer composition, so limits must be set according to the actual isomer ratio of each batch

• Chemical Name: (E)-(1R,1’R)-2,2’-[4-octenedioylbis(oxypropylene)]bis[1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethoxybenzyl)isoquinolinium] dichloride

• Stereochemistry: Mixture of three stereoisomers (trans-trans : cis-trans : cis-cis ≈ 60:35:6), 2 defined stereocenters, 2 undefined stereocenters, 1 defined double-bond configuration (E)

• Solubility: Soluble in water, ethanol, and 1-octanol; reagent-grade solubility in DMSO, water, and ethanol all up to 100 mg/mL; slightly soluble in chloroform and methanol. Hygroscopic

• Partition Coefficient: 0.015 (1-octanol/distilled water system, 25 ℃)

• Ionization Characteristics: Quaternary ammonium salt; fully ionized at the concentrations tested; no pKa can be assigned

• Calculated Physicochemical Parameters: LogP about 2.955; topological polar surface area about 144.9–145 Ų; H-bond donors 0 / acceptors 14; rotatable bonds 30; heavy atom count 76

• Formulation Parameters: Injection pH 3.5–5.5, concentration 2 mg/mL (calculated as mivacurium); Chinese strengths 5 mL:10 mg and 10 mL:20 mg; also available as 10 mL single-dose vials and 20 mL and 50 mL multiple-dose vials containing 0.9% benzyl alcohol

• Storage: Strongly hygroscopic—seal tightly, protect from light, store at 2–8 ℃, do not freeze (Chinese label); some reference standards recommend −20 ℃ under inert gas; the API should be kept in a dry environment

Applications

• Adjunct to general anesthesia (core indication): As a highly selective, short-acting, non-depolarizing neuromuscular blocking agent, used to relax skeletal muscle to facilitate tracheal intubation and mechanical ventilation. Suitable for short surgical procedures, short-to-medium-duration emergency surgery, and ambulatory surgery

• Dosage and administration (adults, intravenous injection): ED95 approximately 0.07 mg/kg (range 0.06–0.09 mg/kg); recommended single-dose range in healthy adults is 0.07–0.25 mg/kg. Duration of neuromuscular block is dose-related: doses of 0.07, 0.15, 0.20, and 0.25 mg/kg produce effective block durations of approximately 13, 16, 20, and 23 minutes, respectively. For doses ≤0.15 mg/kg, injection time may be 5–15 seconds; higher doses should be injected over more than 30 seconds to reduce the risk of cardiovascular reactions

• Tracheal intubation dosing regimens: ① 0.2 mg/kg injected over more than 30 seconds produces good intubating conditions within 2–2.5 minutes; ② 0.25 mg/kg in divided doses (0.15 mg/kg first, then 0.1 mg/kg after 30 seconds) produces good intubating conditions within 1.5–2.0 minutes after the first dose

• Pharmacology and mechanism research: Used for competitive antagonism studies of nicotinic acetylcholine receptors at the neuromuscular junction, plasma cholinesterase hydrolysis kinetics and metabolite evaluation, structure-activity comparison of benzylisoquinolinium versus aminosteroid muscle relaxants, and methodology research on neuromuscular monitoring (TOF, single twitch)

• Formulation and manufacturing: Used for formulation development of injections (2 mg/mL); excipients are hydrochloric acid (for pH adjustment) and water for injection, with no antimicrobial preservative—each vial is for single-patient use; multiple-dose vials contain 0.9% benzyl alcohol. Incompatibilities: do not mix with strongly alkaline solutions (e.g., barbiturate solutions); compatible with 5% dextrose injection, 0.9% sodium chloride injection, 5% dextrose and sodium chloride injection, lactated Ringer’s injection, and 5% dextrose in lactated Ringer’s injection; when diluted to 0.5 mg/mL, it is physically and chemically stable in PVC bags at room temperature for 24 hours. Key manufacturing control points include the ratio and total content of the three stereoisomers, related substances (ester hydrolysis products), pH (3.5–5.5), and moisture (hygroscopicity) control; suitable for analytical method development and validation, stability studies, and GMP scale-up and CMO/CDMO contract manufacturing

Safety Notice: This product is a pharmaceutical active ingredient (API) intended solely for compliant industrial, research, and pharmaceutical manufacturing use; it is not intended for end clinical use or self-medication guidance. The finished product is a prescription drug and must be used by trained anesthesiologists in settings equipped for tracheal intubation, artificial ventilation, and oxygen therapy. Contraindications: patients with known hypersensitivity to mivacurium; pregnant women (no data on use in pregnancy are currently available); patients known or suspected to be homozygous for the atypical plasma cholinesterase gene—because they lack the ability to hydrolyze this product, prolonged neuromuscular block may result. Duration of action may be markedly prolonged in patients with renal or hepatic impairment and in those with reduced plasma cholinesterase activity (e.g., pregnancy, hepatorenal disease, effects of certain drugs). Use with caution in patients allergic to this product or other muscle relaxants. Wear protective gloves, protective clothing, and eye/face protection when handling the API, and avoid dust inhalation; GHS hazard statements include skin irritation (H315), serious eye irritation (H319), and respiratory irritation (H335).

Product information: please contact us. This information is for reference only.