Convulsive effects and pharmacokinetics of laudanosine in the rat.
Laudanosine, which is a degradation product of atracurium, is a convulsant drug in the rat. Laudanosine plasma concentrations were measured by high performance liquid chromatography after administration of both laudanosine and atracurium; protein binding and renal excretion of laudanosine were also determined. A continuous laudanosine infusion of 25 mg kg-1h-1, or less, did not cause convulsions. Eight times ED90 for twitch depression of atracurium gave rise to a laudanosine plasma concentration of less than 8 micrograms ml-1. The convulsive plasma-concentration level for laudanosine was over 17 micrograms ml-1 in the rat. The protein binding of laudanosine was 80%. The kidney excreted 15-20% laudanosine. We conclude that convulsive levels of laudanosine will be very unlikely in any species provided that normal atracurium doses are used no matter how long the procedure.
D000818:Animals; D006339:Heart Rate / Q000187:drug effects; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology* / Q000652:urine; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D011674:Pulse / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced*
D007546:Isoquinolines; C001522:laudanosine