Метокурин

Description

Metokurine is a semisynthetic alkaloid of the benzylisoquinoline series, an O,O-dimethyl derivative of chondrocurarine. Obtained by methylation of d-tubocurarine, the main active principle of curare: two phenolic hydroxyls are converted to methoxy groups, both nitrogen atoms are quaternary. Hence the synonyms dimethylchondrocurarine and O,O'-dimethylchondrocurarine, as well as the catalog entry tubocurarine, 6,6',7',12'-tetramethoxy-2,2,2',2'-tetramethyl-. The dosage form is methocurine iodide.

Basic Attributes

• CAS No: 5152-30-7; accompanying registrations 1397-58-6, 17573-08-9, 23192-76-9, 29605-20-7, 34168-57-5
• Chemical Formula: C40H48N2O6
• Molecular Weight: 652.832
• Exact weight: 652.351
• UNII: V0M92G2U26
• PSA specifications: 55.4
• XLogP3: 6.7

Physico-chemical properties

• Appearance: solid
• Density: 1.1209 (estimated)
• Solubility in water: 6.42 × 10⁻⁶ g/l

The solubility given is for the compound in the form described by the card. The injection preparation was iodide salt, soluble in water, and ampoule forms were built on it.

Stereochemistry and full name

Full systematic name - (13aR,25aS)-2,3,13a,14,15,16,25,25a-octahydro-9,18,19,29-tetramethoxy-1,1,14,14-tetramethyl-13H-4 ,621,24-dietheno-8,12-metheno-1H-pyrido[3',2'14,15][1,11]dioxacycloeicosino[2,3,4-ij]isoquinoline. A macrocyclic framework with two simple ether bridges between aromatic rings fixes the distance between two quaternary nitrogen atoms - it is this distance that determines the ability of the molecule to bind to two receptor subunits at once.

Pharmacological group and mechanism of action

Metokurine is a non-depolarizing (competitive) muscle relaxant with peripheral action. The molecule competes with acetylcholine for nicotinic cholinergic receptors at the end plate of skeletal muscle. Having occupied the receptor, it does not cause the opening of the ion channel, so the end plate potential does not develop and the muscle fiber does not contract. The compound was synthesized by King in 1935 as a trimethylated derivative of d-tubocurarine. Compared to the parent alkaloid, methocurine is more active in most animal species and more selective: side effects, primarily from the cardiovascular system, are less pronounced, but the duration of action is longer.

Clinical Application

• Adjuvant to general anesthesia: relaxation of skeletal muscles during surgery
• Facilitation of tracheal intubation
• Providing artificial ventilation

Paralysis develops 3–5 minutes after intravenous administration. Clinical duration - the time until the amplitude of the muscle response is restored by 25% - is approximately 60-90 minutes, which classifies the drug as a long-acting muscle relaxant: it is suitable for long-term operations and inconvenient for short interventions. The action is stopped by the introduction of anticholinesterase drugs - neostigmine, edrophonium, pyridostigmine. These drugs inhibit the enzyme that breaks down acetylcholine; the concentration of the transmitter in the synaptic cleft increases sharply, and it displaces metocurine from the receptors. The drug is no longer available on the US pharmaceutical market.

Storage and handling

The substance is a potent substance; work with it is carried out under conditions that exclude access to unauthorized persons. Keep the container tightly closed in a cool, dry place, protected from light. When hanging, gloves and safety glasses are used, dust is excluded - getting even small amounts of bis-quaternary muscle relaxant into the body is dangerous by paralyzing the respiratory muscles. Work is carried out where artificial lung ventilation is available.