Muscle relaxant.

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].

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]

Biological Half-Life
3 to 4 hours

Protein Binding
35% of plasma

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Human TDLo intravenously 150 ug/kg Sensory organs and special senses: ptosis; Blood vessels: decreased blood pressure, autonomic nervous system not described; Lungs, pleura or respiration: dyspnea. Journal of Pharmacology and Experimental Therapeutics, 93(109), 1948
Rat LD50 Intraperitoneal injection 370 ug/kg Peripheral nerves and sensation: flaccid paralysis, no anesthesia required (usually neuromuscular blockade); Lungs, pleura or respiration: dyspnea, Journal of Pharmacology and Experimental Therapeutics, 93(109), 1948
Rat Intravenous injection LD50 35 ug/kg Behavior: seizures or effects on the epileptic threshold; Lungs, pleura or respiration: other changes, Journal of Laboratory and Clinical Medicine, 34(516), 1949
Mouse Intravenous injection LD50 230 μg/kg Behavioral manifestations: muscle weakness, Naun-Schmidberg Literature of Experimental Pathology and Pharmacology, 244(493), 1963 [PMID:13987623]
The intravenous LD50 in rabbits was 32 μg/kg. Behavioral findings: seizures or effects on the epilepsy threshold; lung, pleural, or respiratory changes; other changes. Journal of Laboratory and Clinical Medicine, 34(516), 1949.

[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.

Metocurine iodide is an aromatic ether. Metocurine iodide is a benzylisoquinoline competitive non-depolarizing neuromuscular blocking agent. It is used as an adjunct to anesthesia to induce skeletal muscle relaxation and reduce the intensity of muscle contractions during the treatment of seizures. Metocurine iodide carries a moderate risk of inducing histamine release and has some ganglion-blocking activity. Its effectiveness is best assessed when monitoring muscle twitching responses to peripheral nerve stimulation to evaluate the degree of muscle relaxation. Metocurine iodide is no longer marketed in the United States. See also: Metocurine (containing the active ingredient). Indications: For adjunctive anesthesia to induce skeletal muscle relaxation and reduce the intensity of muscle contractions during the treatment of seizures. Mechanism of Action: Metocurine iodide antagonizes the neurotransmitter effect of acetylcholine by competitively binding to cholinergic receptors on the motor endplate. This antagonistic effect can be inhibited by acetylcholinesterase inhibitors such as neostigmine, ethanochlor, and pyridostigmine, thereby reversing neuromuscular blockade.

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Pharmacodynamics
Metocurine iodide is a benzylisoquinoline competitive non-depolarizing neuromuscular blockade. Metocurine iodide carries a moderate risk of inducing histamine release and possesses some ganglion-blocking activity. It is most effective when used to assess muscle relaxation by monitoring muscle twitching responses to peripheral nerve stimulation. Like other non-depolarizing neuromuscular blockades, the onset time of Metocurine iodide decreases with increasing dose, while the duration of maximum effect increases. Repeated administration of a maintenance dose of Metocurine iodide does not have a cumulative effect on the duration of neuromuscular blockade if the patient is allowed to begin recovery before repeat administration. Furthermore, the recovery time after repeat administration does not change with increasing dose. Therefore, relatively regular repeat administration can yield predictable results.

C40H48I2N2O6

906.63

906.16

7601-55-0

5152-30-7 (Parent)

24244

Typically exists as solid at room temperature

267-270

1.377

0

8

4

50

1060

2

[I-].[I-].COc1ccc2CC3c4c(CC[N+]3(C)C)cc(OC)c(OC)c4Oc3ccc(CC4c5cc(Oc1c2)c(OC)cc5CC[N+]4(C)C)cc3

DIGFQJFCDPKEPF-OIUSMDOTSA-L

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

(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

METOCURINE IODIDE; Metubine iodide; 7601-55-0; Dimethylchondrocurarine iodide; Methyl-curarin; Tetrandrini dimethiodidum; Dimethyl tubocurarine iodide; O,O'-Dimethylchondrocurarine diiodide;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)