Laudanosine Explained

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.

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]

Notes and References

1. Fodale V, Santamaria LB . Laudanosine, an atracurium and cisatracurium metabolite . Eur J Anaesthesiol . 19 . 7 . 466–73 . July 2002 . 12113608 . 10.1017/s0265021502000777.
2. Book: https://books.google.com/books?id=KxTKLlac60wC&q=laudanosine&pg=PA55 . The Benzylisoquinoline Alkaloids . Burger A . The Alkaloids: Chemistry and Physiology . 1954 . 2005 . 4 . Manske RH, Holmes HL . 48 . New York . Academic Press . 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 . Interactions between laudanosine, GABA, and opioid subtype receptors: implication for laudanosine seizure activity . Brain Res . 646 . 2 . 235–241 . May 1994 . 8069669 . 10.1016/0006-8993(94)90084-1 . 35031924 .
4. Exley R, Iturriaga-Vásquez P, Lukas RJ, Sher E, Cassels BK, Bermudez I . Evaluation of benzyltetrahydroisoquinolines as ligands for neuronal nicotinic acetylcholine receptors . Br J Pharmacol . 146 . 1 . 15–24 . Sep 2005. 15980871 . 10.1038/sj.bjp.0706307 . 1576253 .
5. Katz Y, Gavish M . Laudanosine does not displace receptor-specific ligands from the benzodiazepinergic or muscarinic receptors . Anesthesiology. 70. 1 . 109–111 . Jan 1989 . 2536252 . 10.1097/00000542-198901000-00020 .