Laudanosine

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

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
CAS Number	2688-77-9 Y
3D model (JSmol)	Interactive image
ChemSpider	66114 N
ECHA InfoCard	100.018.412
EC Number	220-253-2
PubChem CID	73397
UNII	DA7R5WVN48 Y
CompTox Dashboard (EPA)	DTXSID30878577
InChI 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
SMILES CN1CCc2cc(c(cc2[C@@H]1Cc3ccc(c(c3)OC)OC)OC)OC
Properties
Chemical formula	C21H27NO4
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). N verify (what is YN ?) Infobox references

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

1. Fodale V, Santamaria LB (July 2002). "Laudanosine, an atracurium and cisatracurium metabolite". Eur J Anaesthesiol. 19 (7): 466–73. doi:10.1017/s0265021502000777. PMID 12113608.
2. 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.
3. 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.
4. 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.
5. 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.