 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C40H48I2N2O6 |
| Molecular Weight | 906.63 |
| Exact Mass | 906.16 |
| CAS # | 7601-55-0 |
| Related CAS # | 5152-30-7 (Parent) |
| PubChem CID | 24244 |
| Appearance | Typically exists as solid at room temperature |
| Melting Point | 267-270 |
| LogP | 1.377 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 50 |
| Complexity | 1060 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | [I-].[I-].COc1ccc2CC3c4c(CC[N+]3(C)C)cc(OC)c(OC)c4Oc3ccc(CC4c5cc(Oc1c2)c(OC)cc5CC[N+]4(C)C)cc3 |
| InChi Key | DIGFQJFCDPKEPF-OIUSMDOTSA-L |
| InChi Code | InChI=1S/C40H48N2O6.2HI/c1-41(2)17-15-27-22-34(44-6)36-24-30(27)31(41)19-25-9-12-29(13-10-25)47-40-38-28(23-37(45-7)39(40)46-8)16-18-42(3,4)32(38)20-26-11-14-33(43-5)35(21-26)48-36;;/h9-14,21-24,31-32H,15-20H2,1-8H3;2*1H/q+2;;/p-2/t31-,32+;;/m0../s1 |
| Chemical Name | (1S,16R)-9,10,21,25-tetramethoxy-15,15,30,30-tetramethyl-7,23-dioxa-15,30-diazoniaheptacyclo[22.6.2.23,6.18,12.118,22.027,31.016,34]hexatriaconta-3(36),4,6(35),8(34),9,11,18(33),19,21,24,26,31-dodecaene;diiodide |
| Synonyms | METOCURINE IODIDE; Metubine iodide; 7601-55-0; Dimethylchondrocurarine iodide; Methyl-curarin; Tetrandrini dimethiodidum; Dimethyl tubocurarine iodide; O,O'-Dimethylchondrocurarine diiodide; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Muscle relaxant. |
| ln Vitro | In isolated canine heart muscle, metubine (>15.0×10-3 g/L) causes dose-dependent declines in the isometric force (F) and maximum velocity of force development (dF/dt)[1]. |
| ln Vivo | The inotropic effects of five non-depolarizing muscle relaxants were examined using an isolated canine heart muscle preparation. Except for fazadinium, all drugs were studied in their commercially available forms. d-Tubocurarine chloride (dTc) and metocurine iodide (MTC) produced dose-dependent decreases in isometric force (F) and the maximum velocity of force development (dF/dt) at concentrations greater than 22.5 x 10(-3) g/L for dTc and greater than 15.0 x 10(-3) g/L for MTC, concentrations which are 3 and 6 times higher than estimated clinical serum concentrations, respectively. Myocardial depression was about 3 times less with MTC than with dTc at equipotent concentrations. The degree of depression in F and dF/dt produced by MTC was almost identical with that produced by phenol, a preservative of MTC, indicating that MTC-induced myocardial depression may be due to the effect of the preservative. Pancuronium bromide (PC) produced a dose-dependent increase in F and dF/dt and decrease in the time to peak force. PC-induced changes in F, dF/dt, and time to peak force were inhibited by administration of propranolol 10(-6) M. The results indicate that PC possesses a positive inotropic effect mediated by beta-adrenergic stimulation. Alcuronium chloride did not change F or dF/dt at concentrations from 5.0 x 10(-3) to 60.0 x 10(-3) g/L. Frazadinium bromide increased F and dF/ dt slightly at a low concentration (1.875 x 10(-2) g/L), but further increases in its concentration returned the values of F and dF/dt to control levels. F and dF/dt were not altered in vitro by concentrations of relaxants that would be anticipated in plasma in vivo in patients given clinically effective doses of 0.3 mg/kg of dTc, 0.1 mg/kg of MTC or PC, 0.2 mg/kg of alcuronium chloride, or 0.75 mg/kg of fazadinium bromide.[1] |
| ADME/Pharmacokinetics |
Biological Half-Life 3 to 4 hours |
| Toxicity/Toxicokinetics |
Protein Binding 35% in plasma man TDLo intravenous 150 ug/kg SENSE ORGANS AND SPECIAL SENSES: PTOSIS: EYE; VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION; LUNGS, THORAX, OR RESPIRATION: DYSPNEA Journal of Pharmacology and Experimental Therapeutics., 93(109), 1948 rat LD50 intraperitoneal 370 ug/kg PERIPHERAL NERVE AND SENSATION: FLACCID PARALYSIS WITHOUT ANESTHESIA (USUALLY NEUROMUSCULAR BLOCKAGE); LUNGS, THORAX, OR RESPIRATION: DYSPNEA Journal of Pharmacology and Experimental Therapeutics., 93(109), 1948 rat LD50 intravenous 35 ug/kg BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD; LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES Journal of Laboratory and Clinical Medicine., 34(516), 1949 mouse LD50 intravenous 230 ug/kg BEHAVIORAL: MUSCLE WEAKNESS Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie., 244(493), 1963 [PMID:13987623] rabbit LD50 intravenous 32 ug/kg BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD; LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES Journal of Laboratory and Clinical Medicine., 34(516), 1949 |
| References |
[1]. Iwatsuki N, et al. Inotropic effects of non-depolarizing muscle relaxants in isolated canine heart muscle. Anesth Analg. 1980 Oct;59(10):717-21. [2]. Durant NN, et al. A comparison of the neuromuscular and autonomic blocking activities of (+)-tubocurarine and its N-methyl and O,O,N-trimethyl analogues. Eur J Pharmacol. 1977 Dec 15;46(4):297-302. |
| Additional Infomation |
Metocurine iodide is an aromatic ether. Metocurine iodide is a benzylisoquinolinium competitive nondepolarizing neuromuscular blocking agent. It is used as an anesthesia adjunct to induce skeletal muscle relaxation and to reduce the intensity of muscle contractions in convulsive therapy Metocurine iodide has a moderate risk of inducing histamine release and has some ganglion blocking activity. Metocurine iodide can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored to assess degree of muscle relaxation. Metocurine Iodide is no longer available on the US market. See also: Metocurine (has active moiety). Drug Indication For use as an anesthesia adjunct to induce skeletal muscle relaxation and to reduce the intensity of muscle contractions in convulsive therapy. Mechanism of Action Metocurine iodide antagonizes the neurotransmitter action of acetylcholine by binding competitively with cholinergic receptor sites on the motor end-plate. This antagonism is inhibited, and neuromuscular block reversed, by acetylcholinesterase inhibitors such as neostigmine, edrophonium, and pyridostigmine. Pharmacodynamics Metocurine iodide is a benzylisoquinolinium competitive nondepolarizing neuromuscular blocking agent. Metocurine iodide has a moderate risk of inducing histamine release and has some ganglion blocking activity. Metocurine iodide can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored to assess degree of muscle relaxation. As with other nondepolarizing neuromuscular blockers, the time to onset of paralysis decreases and the duration of maximum effect increases with increasing doses of metocurine iodide. Repeated administration of maintenance doses of metocurine iodide has no cumulative effect on the duration of neuromuscular block if recovery is allowed to begin prior to repeat dosing. Moreover, the time needed to recover from repeat doses does not change with additional doses. Repeat doses can therefore be administered at relatively regular intervals with predictable results. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1030 mL | 5.5149 mL | 11.0299 mL | |
| 5 mM | 0.2206 mL | 1.1030 mL | 2.2060 mL | |
| 10 mM | 0.1103 mL | 0.5515 mL | 1.1030 mL |