LAUDANOSINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H27NO4
Molecular Weight	357.4434
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(C=C1OC)[C@H](CC3=CC(OC)=C(OC)C=C3)N(C)CC2

InChI

InChIKey=KGPAYJZAMGEDIQ-KRWDZBQOSA-N

InChI=1S/C21H27NO4/c1-22-9-8-15-12-20(25-4)21(26-5)13-16(15)17(22)10-14-6-7-18(23-2)19(11-14)24-3/h6-7,11-13,17H,8-10H2,1-5H3/t17-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12113608 | https://www.ncbi.nlm.nih.gov/pubmed/8069669

Laudanosine, a potentially epileptogenic metabolite of the neuromuscular relaxant atracurium besylate with potentially toxic effects. Laudanosine is a non-competitive and voltage-dependent inhibitor of alpha7, alpha4beta2 or alpha4beta4 nicotinic acetylcholine receptors, opioid mu 1 type receptors and possesses a low-affinity to the GABA receptors, but didn’t interact with the benzodiazepine or muscarinic receptors.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Potency
gamma-aminobutyric acid (GABA) receptors 1 Target ID: gamma-aminobutyric acid (GABA) receptors Sources: https://www.ncbi.nlm.nih.gov/pubmed/8069669	Binding Agent 1064
Neuronal acetylcholine receptor; alpha4/beta2 76 Target ID: CHEMBL1907589 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15980871	Inhibitor 8297
Mu-type opioid receptor 61 Target ID: P35372\|\|\|G8XRH8\|\|\|Q5TDA1\|\|\|Q9UN57 Gene ID: 4988.0 Gene Symbol: OPRM1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/8069669	Inhibitor 8297	2.7 µM [Ki]
Neuronal acetylcholine receptor; alpha4/beta4 7 Target ID: CHEMBL1907591 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15980871	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

PubMed

Title	Date	PubMed
Laudanosine and atracurium concentrations in a patient receiving long-term atracurium infusion.	1998 Jan	9428564
Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine.	2001 Apr	11379686
Concentration-effect relationship of cisatracurium at three different dose levels in the anesthetized patient.	2001 Aug	11506100
The pharmacokinetics of cisatracurium in patients with acute respiratory distress syndrome.	2001 Aug	11473869
Pharmacokinetic-pharmacodynamic modeling of atracurium in intensive care patients.	2001 Jan	11144993
Inhibitory effects of ethaverine, a homologue of papaverine, on monoamine oxidase activity in mouse brain.	2001 Jul	11456127
Does ester hydrolysis change the in vitro degradation rate of cisatracurium and atracurium?	2002 Apr	12066733
Pharmacodynamics and atracurium and laudanosine concentrations during a fixed continuous infusion of atracurium in mechanically ventilated patients with acute respiratory distress syndrome.	2002 Aug	12180578
Laudanosine, an atracurium and cisatracurium metabolite.	2002 Jul	12113608
Colominic acid: a novel chiral selector for capillary electrophoresis of basic drugs.	2002 Jul 12	12198966
Cerebrospinal fluid concentrations of atracurium, laudanosine and vecuronium following clinical subarachnoid hemorrhage.	2002 Nov	12421196
Methyl-laudanosine: a new pharmacological tool to investigate the function of small-conductance Ca(2+)-activated K(+) channels.	2002 Sep	12183678
Aporphine alkaloids from Guatteria spp. with leishmanicidal activity.	2003 Jul	12898429
The possible neuroprotective effect of laudanosine, an atracurium and cisatracurium metabolite.	2003 Jul	12803601
Transformation of opium poppy (Papaver somniferum L.) with antisense berberine bridge enzyme gene (anti-bbe) via somatic embryogenesis results in an altered ratio of alkaloids in latex but not in roots.	2004 Dec	15672841
Instability of pancuronium in postmortem blood and liver taken after a fatal intramuscular Pavulon injection.	2004 Jul 16	15240043
The insulin pump as murder weapon: a case report.	2004 Jun	15166770
Identification and quantitation of six non-depolarizing neuromuscular blocking agents by LC-MS in biological fluids.	2004 Mar	15068563
The GC-MS detection and characterization of reticuline as a marker of opium use.	2004 Mar 10	15036439
The GC-MS detection and characterization of reticuline as a marker of opium use.	2004 May 28	15272474
The efficient synthesis of morphinandienone alkaloids by using a combination of hypervalent iodine(III) reagent and heteropoly acid.	2004 Oct 11	15372696
Perinatal neuroprotection by muscle relaxants against hypoxic-ischemic lesions: is it a possible hypothesis?	2005 Aug	16203600
SK channels control the firing pattern of midbrain dopaminergic neurons in vivo.	2005 Dec	16367777
Synthesis and biological evaluation of N-methyl-laudanosine iodide analogues as potential SK channel blockers.	2005 Feb 15	15670929
Evaluation of benzyltetrahydroisoquinolines as ligands for neuronal nicotinic acetylcholine receptors.	2005 Sep	15980871
Chiral separation of norlaudanosoline, laudanosoline, laudanosine, chlorthalidone, and three benzoin derivatives using amino acid based molecular micelles.	2006 Feb	16620496
Anesthesiologist suicide with atracurium.	2006 Mar	16620544
Simultaneous determination of atracurium and its metabolite laudanosine in post-mortem fluids by liquid chromatography/multiple-stage mass spectrometry on an ion trap.	2007	17676709
Bioactive constituents of the roots of Polyalthia cerasoides.	2007 Sep	17845001
Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury.	2008	19040780
Applicability of ultra-performance liquid chromatography-tandem mass spectrometry for heroin profiling.	2008 Apr 25	18374345
[Absorption of papaverine, laudanosine and cepharanthine across human intestine by using human Caco-2 cells monolayers model].	2008 Feb	18507350
Bis-tetrahydroisoquinoline derivatives: AG525E1, a new step in the search for non-quaternary non-peptidic small conductance Ca(2+)-activated K(+) channel blockers.	2008 Jun 1	18436444
Use of intrathecal and intravenous clonidine in a case of severe tetanus with acute renal failure.	2009 Apr	20640124
Laudanosine has no effects on respiratory activity but induces non-respiratory excitement activity in isolated brainstem-spinal cord preparation of neonatal rats.	2010	20217344
The biosynthesis of papaverine proceeds via (S)-reticuline.	2010 Aug	20494383
Determination of atracurium, cisatracurium and mivacurium with their impurities in pharmaceutical preparations by liquid chromatography with charged aerosol detection.	2010 Feb 19	20036772
Evaluation of the enantioselectivity of glycogen-based dual chiral selector systems towards basic drugs in capillary electrophoresis.	2010 Nov 5	20926087

Sample Use Guides

In Vivo Use Guide

In mice and rats: i.v. bolus doses of laudanosine 10-20 mg kg-1, caused convulsions and hind limb extensions

Route of Administration: Intravenous

In Vitro Use Guide

Laudanosine was almost ineffective at [3H]muscimol binding to high-affinity GABA receptors (IC50 = 100 microM). However, laudanosine displayed an inhibitory effect at the low-affinity GABA receptors labeled by [3H]bicuculline methochloride, with an IC50 value of 10 microM. At the opioid receptor subtype, laudanosine lowered radiolabeled opioid binding at the mu 1, mu 2, delta, kappa 1, and kappa 3 receptors with Ki values of 2.7, 13, 5.5, 21, and 24 microM, respectively.

Name

Type

Language

LAUDANOSINE

Official Name

English

NSC-35045

Code

English

1,2,3,4-TETRAHYDRO-6,7-DIMETHOXY-2-METHYL-1-VERATRYLISOQUINOLINE

Systematic Name

English

Isoquinoline, 1-[(3,4-dimethoxyphenyl)methyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-, (1S)-

Systematic Name

English

LAUDANOSINE [INCI]

Common Name

English

(1S)-1-((3,4-DIMETHOXYPHENYL)METHYL)-1,2,3,4-TETRAHYDRO-6,7-DIMETHOXY-2-METHYLISOQUINOLINE

Systematic Name

English

LAUDANOSINE [MI]

Common Name

English

(S)-(+)-LAUDANOSINE

Common Name

English

N-METHYLTETRAHYDROPAPAVERINE

Common Name

English

Code System Code Type Description

CAS

2688-77-9