Laudanosine
Names
Preferred IUPAC name
(1S )-1-[(3,4-Dimethoxyphenyl)methyl]-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline
Other names
N -Methyl-1,2,3,4-tetrahydropapaverine
Identifiers
ChemSpider
ECHA InfoCard
100.018.412
EC Number
UNII
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
N Key: KGPAYJZAMGEDIQ-KRWDZBQOSA-N
N InChI=1/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
Key: KGPAYJZAMGEDIQ-KRWDZBQOBO
CN1CCc2cc(c(cc2[C@@H]1Cc3ccc(c(c3)OC)OC)OC)OC
Properties
C 21 H 27 N O 4
Molar mass
357.450 g·mol−1
Melting point
89 °C (192 °F; 362 K)
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Laudanosine or N -methyltetrahydropapaverine is a recognized metabolite[ 1] of atracurium and cisatracurium . Laudanosine decreases the seizure threshold, and thus it can induce seizures if present at sufficient threshold concentrations; however such concentrations are unlikely to be produced consequent to chemodegradable metabolism of clinically administered doses of cisatracurium or atracurium .
Capsule of Papaver somniferum showing latex (opium) exuding from incision. Laudanosine occurs naturally in small amounts (0.1%) in opium.
Laudanosine also occurs naturally in minute amounts (0.1%) in opium , from which it was first isolated in 1871.[ 2] Partial dehydrogenation of laudanosine will lead to papaverine , the alkaloid found in the opium poppy plant (Papaver somniferum ).
Laudanosine is a benzyltetrahydroisoquinoline alkaloid . It has been shown to interact with GABA receptors , glycine receptors , opioid receptors , and nicotinic acetylcholine receptors ,[ 1] [ 3] [ 4] but not benzodiazepine or muscarinic receptors , which are also involved in epilepsy and other types of seizures.[ 5]
References
^ a b Fodale V, Santamaria LB (July 2002). "Laudanosine, an atracurium and cisatracurium metabolite". Eur J Anaesthesiol . 19 (7): 466–73. doi :10.1017/s0265021502000777 (inactive 1 November 2024). PMID 12113608 . {{cite journal }}
: CS1 maint: DOI inactive as of November 2024 (link )
^ Burger A (2005) [1954]. "The Benzylisoquinoline Alkaloids" . In Manske RH, Holmes HL (eds.). The Alkaloids: Chemistry and Physiology . Vol. 4. New York: Academic Press. p. 48. ISBN 0-12-469504-3 . Retrieved September 18, 2008 through Google Book Search .
^ Katz Y, Weizman A, Pick CG, Pasternak GW, Liu L, Fonia O, Gavish M (May 1994). "Interactions between laudanosine, GABA, and opioid subtype receptors: implication for laudanosine seizure activity". Brain Res . 646 (2): 235–241. doi :10.1016/0006-8993(94)90084-1 . PMID 8069669 . S2CID 35031924 .
^ Exley R, Iturriaga-Vásquez P, Lukas RJ, Sher E, Cassels BK, Bermudez I (Sep 2005). "Evaluation of benzyltetrahydroisoquinolines as ligands for neuronal nicotinic acetylcholine receptors" . Br J Pharmacol . 146 (1): 15–24. doi :10.1038/sj.bjp.0706307 . PMC 1576253 . PMID 15980871 .
^ Katz Y, Gavish M (Jan 1989). "Laudanosine does not displace receptor-specific ligands from the benzodiazepinergic or muscarinic receptors". Anesthesiology . 70 (1): 109–111. doi :10.1097/00000542-198901000-00020 . PMID 2536252 .
Ionotropic
GABAA Tooltip γ-Aminobutyric acid A receptor
Positive modulators (abridged; see here for a full list): α-EMTBL
Alcohols (e.g., drinking alcohol , 2M2B )
Anabolic steroids
Avermectins (e.g., ivermectin )
Barbiturates (e.g., phenobarbital )
Benzodiazepines (e.g., diazepam )
Bromide compounds (e.g., potassium bromide )
Carbamates (e.g., meprobamate )
Carbamazepine
Chloralose
Chlormezanone
Clomethiazole
Dihydroergolines (e.g., ergoloid (dihydroergotoxine) )
Etazepine
Etifoxine
Fenamates (e.g., mefenamic acid )
Flavonoids (e.g., apigenin , hispidulin )
Fluoxetine
Flupirtine
Imidazoles (e.g., etomidate )
Kava constituents (e.g., kavain )
Lanthanum
Loreclezole
Monastrol
Neuroactive steroids (e.g., allopregnanolone , cholesterol , THDOC )
Niacin
Niacinamide
Nonbenzodiazepines (e.g., β-carbolines (e.g., abecarnil ), cyclopyrrolones (e.g., zopiclone ), imidazopyridines (e.g., zolpidem ), pyrazolopyrimidines (e.g., zaleplon ))
Norfluoxetine
Petrichloral
Phenols (e.g., propofol )
Phenytoin
Piperidinediones (e.g., glutethimide )
Propanidid
Pyrazolopyridines (e.g., etazolate )
Quinazolinones (e.g., methaqualone )
Retigabine (ezogabine)
ROD-188
Skullcap constituents (e.g., baicalin )
Stiripentol
Sulfonylalkanes (e.g., sulfonmethane (sulfonal) )
Topiramate
Valerian constituents (e.g., valerenic acid )
Volatiles /gases (e.g., chloral hydrate , chloroform , diethyl ether , paraldehyde , sevoflurane )
Negative modulators: 1,3M1B
3M2B
11-Ketoprogesterone
17-Phenylandrostenol
α3IA
α5IA (LS-193,268)
β-CCB
β-CCE
β-CCM
β-CCP
β-EMGBL
Anabolic steroids
Amiloride
Anisatin
β-Lactams (e.g., penicillins , cephalosporins , carbapenems )
Basmisanil
Bemegride
Bicyclic phosphates (TBPS , TBPO , IPTBO )
BIDN
Bilobalide
Bupropion
CHEB
Chlorophenylsilatrane
Cicutoxin
Cloflubicyne
Cyclothiazide
DHEA
DHEA-S
Dieldrin
(+)-DMBB
DMCM
DMPC
EBOB
Etbicyphat
FG-7142 (ZK-31906)
Fiproles (e.g., fipronil )
Flavonoids (e.g., amentoflavone , oroxylin A )
Flumazenil
Fluoroquinolones (e.g., ciprofloxacin )
Flurothyl
Furosemide
Golexanolone
Iomazenil (123 I)
IPTBO
Isopregnanolone (sepranolone)
L-655,708
Laudanosine
Lindane
MaxiPost
Morphine
Morphine-3-glucuronide
MRK-016
Naloxone
Naltrexone
Nicardipine
Nonsteroidal antiandrogens (e.g., apalutamide , bicalutamide , enzalutamide , flutamide , nilutamide )
Oenanthotoxin
Pentylenetetrazol (pentetrazol)
Phenylsilatrane
Picrotoxin (i.e., picrotin , picrotoxinin and dihydropicrotoxinin )
Pregnenolone sulfate
Propybicyphat
PWZ-029
Radequinil
Ro 15-4513
Ro 19-4603
RO4882224
RO4938581
Sarmazenil
SCS
Suritozole
TB-21007
TBOB
TBPS
TCS-1105
Terbequinil
TETS
Thujone
U-93631
Zinc
ZK-93426
GABAA -ρ Tooltip γ-Aminobutyric acid A-rho receptor
Metabotropic
GABAB Tooltip γ-Aminobutyric acid B receptor
Receptor (ligands )
GlyR Tooltip Glycine receptor
Positive modulators: Alcohols (e.g., brometone , chlorobutanol (chloretone) , ethanol (alcohol) , tert -butanol (2M2P) , tribromoethanol , trichloroethanol , trifluoroethanol )
Alkylbenzene sulfonate
Anandamide
Barbiturates (e.g., pentobarbital , sodium thiopental )
Chlormethiazole
D12-116
Dihydropyridines (e.g., nicardipine )
Etomidate
Ginseng constituents (e.g., ginsenosides (e.g., ginsenoside-Rf ))
Glutamic acid (glutamate)
Ivermectin
Ketamine
Neuroactive steroids (e.g., alfaxolone , pregnenolone (eltanolone) , pregnenolone acetate , minaxolone , ORG-20599 )
Nitrous oxide
Penicillin G
Propofol
Tamoxifen
Tetrahydrocannabinol
Triclofos
Tropeines (e.g., atropine , bemesetron , cocaine , LY-278584 , tropisetron , zatosetron )
Volatiles /gases (e.g., chloral hydrate , chloroform , desflurane , diethyl ether (ether) , enflurane , halothane , isoflurane , methoxyflurane , sevoflurane , toluene , trichloroethane (methyl chloroform) , trichloroethylene )
Xenon
Zinc
Antagonists: 2-Aminostrychnine
2-Nitrostrychnine
4-Phenyl-4-formyl-N-methylpiperidine
αEMBTL
Bicuculline
Brucine
Cacotheline
Caffeine
Colchicine
Colubrine
Cyanotriphenylborate
Dendrobine
Diaboline
Endocannabinoids (e.g., 2-AG , anandamide (AEA) )
Gaboxadol (THIP)
Gelsemine
iso-THAZ
Isobutyric acid
Isonipecotic acid
Isostrychnine
Laudanosine
N-Methylbicuculline
N-Methylstrychnine
N,N-Dimethylmuscimol
Nipecotic acid
Pitrazepin
Pseudostrychnine
Quinolines (e.g., 4-hydroxyquinoline , 4-hydroxyquinoline-3-carboxylic acid , 5,7-CIQA , 7-CIQ , 7-TFQ , 7-TFQA )
RU-5135
Sinomenine
Strychnine
Thiocolchicoside
Tutin
Negative modulators: Amiloride
Benzodiazepines (e.g., bromazepam , clonazepam , diazepam , flunitrazepam , flurazepam )
Corymine
Cyanotriphenylborate
Daidzein
Dihydropyridines (e.g., nicardipine , nifedipine , nitrendipine )
Furosemide
Genistein
Ginkgo constituents (e.g., bilobalide , ginkgolides (e.g., ginkgolide A , ginkgolide B , ginkgolide C , ginkgolide J , ginkgolide M ))
Imipramine
NBQX
Neuroactive steroids (e.g., 3α-androsterone sulfate , 3β-androsterone sulfate , deoxycorticosterone , DHEA sulfate , pregnenolone sulfate , progesterone )
Opioids (e.g., codeine , dextromethorphan , dextrorphan , levomethadone , levorphanol , morphine , oripavine , pethidine , thebaine )
Picrotoxin (i.e., picrotin and picrotoxinin )
PMBA
Riluzole
Tropeines (e.g., bemesetron , LY-278584 , tropisetron , zatosetron )
Verapamil
Zinc
NMDAR Tooltip N-Methyl-D-aspartate receptor
Transporter (blockers )
GlyT1 Tooltip Glycine transporter 1 GlyT2 Tooltip Glycine transporter 2
nAChRs Tooltip Nicotinic acetylcholine receptors
Agonists (and PAMs Tooltip positive allosteric modulators )
5-HIAA
6-Chloronicotine
A-84,543
A-366,833
A-582,941
A-867,744
ABT-202
ABT-418
ABT-560
ABT-894
Acetylcholine
Altinicline
Anabasine
Anatabine
Anatoxin-a
AR-R17779
Bephenium hydroxynaphthoate
Butinoline
Butyrylcholine
Carbachol
Choline
Choline m-bromophenyl ether
Cotinine
Cytisine
Decamethonium
Desformylflustrabromine
Dianicline
Dimethylphenylpiperazinium
Epibatidine
Epiboxidine
Ethanol (alcohol)
Ethoxysebacylcholine
EVP-4473
EVP-6124
Galantamine
GTS-21
Ispronicline
Ivermectin
JNJ-39393406
Levamisole
Lobeline
MEM-63,908 (RG-3487)
Morantel
Nicotine (tobacco )
NS-1738
PHA-543,613
PHA-709,829
PNU-120,596
PNU-282,987
Pozanicline
Pyrantel
Rivanicline
RJR-2429
Sazetidine A
SB-206553
Sebacylcholine
SIB-1508Y
SIB-1553A
SSR-180,711
Suberyldicholine
Suxamethonium (succinylcholine)
Suxethonium (succinyldicholine)
TC-1698
TC-1734
TC-1827
TC-2216
TC-5214
TC-5619
TC-6683
Tebanicline
Tribendimidine
Tropisetron
UB-165
Varenicline
WAY-317,538
XY-4083
Antagonists (and NAMs Tooltip negative allosteric modulators )
Precursors (and prodrugs )