Effect of atracurium and laudanosine on the release of 3H-noradrenaline.
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.
Kinjo
M
M
Department of Anesthesiology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 10467.
Nagashima
H
H
Vizi
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ES
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
D007546:Isoquinolines; D011968:Receptors, Histamine; D011976:Receptors, Muscarinic; D001279:Atracurium; D009892:Opium; C001522:laudanosine; D009638:Norepinephrine