tubocurarine

Tubocurarine

Systematic (IUPAC) name
6,6'-dimethoxy-2,2,2',2'-tetramethyltubocuraran-2,2'-diium-7',12'-diol
Identifiers
CAS number	57-95-4 (chloride hydrochloride) 6989-98-6 (chloride hydrochloride pentahydrate)
ATC code	M03AA02
PubChem	6000
DrugBank	APRD00176
ChemSpider	5778
Chemical data
Formula	C37H42Cl2N2O6
Mol. mass	624.765 g/mol
SMILES	eMolecules & PubChem
Synonyms	(1S,16R)-9,21-dihydroxy-10,25-dimethoxy-15,15,30-trimethyl-7,23-dioxa-15,30-diazaheptacyclo[22.6.2.23,6.18,12.118,22.027,31.016,34]hexatriaconta-3,5,8(34),9,11,18(33),19,21,24,26,31,35-dodecaene-15,30-diium
Pharmacokinetic data
Bioavailability	?
Protein binding	50%
Metabolism	?
Half life	1-2 Hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status	banned
Routes	I.V.
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Tubocurarine chloride is an alkaloid of the benzylisoquinoline type. It is an antagonist of nicotinic neuromuscular acetylcholine receptors^[1] that is used to paralyse patients undergoing anaesthesia.

History

It is one of the chemicals that can be obtained from curare, itself an extract of Chondrodendron tomentosum, a plant found in South American jungles which is used as a source of arrow poison. Native Indians hunting animals with this poison were able to eat the animal's contaminated flesh without being affected by the toxin because tubocurarine cannot easily cross mucous membranes and is thus inactive orally.

Medically, first used in 1912. Introduced in anaesthesia in 1942. The correct chemical structure was only elucidated circa 1970, even though the plant had been known since the Spanish Conquest.

The word curare comes from the South American Indian name for the arrow poison: "ourare". Presumably the initial syllable was pronounced with a heavy glottal stroke. Tubocurarine is so called because the plant samples containing it were first shipped to Europe in tubes.

Today, tubocurarine has fallen into disuse in western medicine, as safer synthetic alternatives such as atracurium are available.

Biosynthesis

Tubocurarine biosynthesis involves a radical coupling of two enantiomeric tetrahydrobenzylisoquinolines, more specifically, the two enantiomers of N-methyl-coclaurine. (R) and (S)-N-methyl-coclaurine come from a Mannich-like reaction between dopamine and 4-hydroxyphenyl-acetaldehyde, facilitated by norcoclaurine synthase (NCS). Both dopamine and 4-hydroxyphenylacetyladehyde originate from L-tyrosine. The biosynthetic pathway is described in more detail in the figures. Methylation of the amine and hydroxyl substituents are facilitated by S-adenosyl methionine (SAM). ^[2]

(S)-norcoclaurine is derived from two tyrosine molecules after decarboxylation.

Compound 6 to compound 7 requires two methylations by SAM at the hydroxyl and amine position.

Other names

d-Tubocurarine. Tubocurarin. Tubocurarinum. Delacurarine. Tubarine. Metubine. Jex

HSDB 2152. Isoquinoline Alkaloid. Tubadil. Mecostrin. Intracostin. Intocostrin.

References

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