Диметилтубокурарин

Description

Dimethyltubocurarine (metokurine) is a semi-synthetic derivative of the natural alkaloid d-tubocurarine, a competitive non-depolarizing muscle relaxant. The molecule blocks nicotinic acetylcholine receptors at the neuromuscular junction, preventing the binding of acetylcholine and causing flaccid paralysis of skeletal muscles without loss of consciousness and pain sensitivity.

Basic Attributes

• CAS No.: 35-67-6
• Chemical formula: C39H45N2O6+
• Molecular Weight: 637.797
• Exact weight: 637.328
• UNII: 947TXZ810I
• ATC code (ATX): M - musculoskeletal system
• PSA specifications: 58.6
• XLogP3: 6.7

Scope of application

Historically, it was used as an adjunct to general anesthesia to relax skeletal muscles during surgery, as well as to reduce the intensity of muscle contractions during electroconvulsive therapy. It is more potent than natural d-tubocurarine, with a similar duration of effect. With the advent of modern non-depolarizing muscle relaxants (rocuronium, vecuronium), which have a lower histamine-releasing effect, a shorter action time and better hemodynamic stability, dimethyltubocurarine has lost its clinical significance. Registration of a drug based on methocurine iodide was revoked in the United States in 2001, and in Canada the product was withdrawn from the market in 1998.

Mechanism of action

As a competitive antagonist of nicotinic cholinergic receptors of the postsynaptic membrane of the neuromuscular junction, the substance blocks the binding of acetylcholine without causing depolarization of the membrane. As a result, an action potential is not formed on the muscle fiber, and the muscle remains relaxed until the blocker is replaced by endogenous acetylcholine or an antidote (cholinesterase inhibitor) is administered.

Storage and historical significance

As a compound derived from the plant alkaloid curare (Chondrodendron tomentosum), it is historically of interest for the pharmacology of neuromuscular transmission and the history of anesthesiology - metocurine was one of the first synthetic improvements to the natural tubocurarine, used by South American Indians as a component of arrow poison. Today the substance is not produced or used in clinical practice; it is of interest primarily for research and historical-pharmacological purposes.

Side effects leading to discontinuation of use

Like other benzylisoquinoline muscle relaxants, methocurine can cause the release of histamine from mast cells, which is clinically manifested by hypotension, tachycardia, bronchospasm and cutaneous erythema. It was this feature of the class that became one of the key reasons why anesthesiologists switched to aminosteroid muscle relaxants of subsequent generations - rocuronium and vecuronium - which have a significantly lower histamine-releasing potential with comparable effectiveness in blocking neuromuscular transmission.

Place in the history of pharmacology

The discovery of the mechanism of action of curare and its derivatives, including metocurine, played a key role in the development of modern anesthesiology - for the first time it allowed surgeons to obtain controlled and reversible relaxation of skeletal muscles independent of the depth of anesthesia, which reduced the doses of general anesthetics and the associated risks.