title: Effect of atracurium and laudanosine on the release of 3H-noradrenaline.
abstract: We examined the effects of atracurium and its breakdown product, laudanosine, on resting and stimulation-evoked release of 3H-noradrenaline (3H-NA) from sympathetic axon terminals of isolated right atria of guinea pigs. Both atracurium 1-100 mumol litre-1 and laudanosine 1-50 mumol litre-1 enhanced the release of 3H-NA evoked by field stimulation (2 Hz, 24 stimuli), but did not affect resting release. When the production of laudanosine from atracurium was inhibited by maintaining the atracurium solution at 4 degrees C, atracurium did not enhance the release of 3H-NA as occurred when it was kept at 37 degrees C. However, atracurium antagonized the inhibitory effect of oxotremorine on release of 3H-NA, whereas laudanosine did not. These data suggest that atracurium possesses an antimuscarinic effect. Its metabolite, laudanosine, in concentrations which would be expected following prolonged administration of atracurium, produced a marked increase in release of 3H-NA. This effect of laudanosine may explain some of the unwanted effects seen following administration of atracurium.
authors.affiliation: Department of Anesthesiology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 10467.
authors.forename: M
authors.initials: M
authors.lastname: Kinjo
authors.forename: H
authors.initials: H
authors.lastname: Nagashima
authors.forename: E S
authors.initials: ES
authors.lastname: Vizi
mesh_terms: D000818:Animals; D001279:Atracurium / Q000494:pharmacology*; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D009892:Opium / Q000494:pharmacology*; D011968:Receptors, Histamine / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007546:Isoquinolines; D011968:Receptors, Histamine; D011976:Receptors, Muscarinic; D001279:Atracurium; D009892:Opium; C001522:laudanosine; D009638:Norepinephrine