Disease relevance of NSC35045

• Hence, it appears unlikely that toxic concentrations of laudanosine would be reached, even in a critically ill patient [1].
• Effect of renal failure on laudanosine excretion in man [2].
• Cardiovascular and neurological effects of laudanosine. Studies in mice and rats, and in conscious and anaesthetized dogs [3].
• Electroencephalographic effects of laudanosine in an animal model of epilepsy [4].
• Thus, laudanosine accumulation and related CNS or cardiovascular toxicity seem unlikely following atracurium administration in the anephric patient [5].

High impact information on NSC35045

• From pH 6.4 to 7.8 there was a 6.5-fold increase in the rate of degradation of cisatracurium and, on a molar basis, the final decomposition product laudanosine accounted for all of the drug [6].
• Atracurium and laudanosine concentrations were measured by HPLC [7].
• The authors determined the pharmacokinetics (including transfer into cerebrospinal fluid [CSF]) and the cardiovascular and central nervous system (CNS) effects of laudanosine, a metabolite of atracurium [8].
• Mean arterial blood pressure decreased significantly to 86% of control levels at 1 min following administration of laudanosine (1 mg . kg-1 iv) and returned to control levels 4 min later.(ABSTRACT TRUNCATED AT 250 WORDS)[8]
• Pharmacokinetics of 1R-cis 1'R-cis atracurium besylate (51W89) and plasma laudanosine concentrations in health and chronic renal failure [9].

Chemical compound and disease context of NSC35045

• CONCLUSION: Significant concentrations of atracurium and laudanosine but not of vecuronium were detected in the CSF of patients during and immediately after intracranial aneurysm surgery [10].

Biological context of NSC35045

• Laudanosine accumulation could be observed in all patients before transplantation, but kinetics returned to normal after successful transplantation [11].
• Saturation studies of mu 1, mu 2, delta, and kappa 3 sites in the presence of laudanosine revealed competitive interactions, with increases in the apparent Kd values but without significant changes in the maximal numbers of binding sites [12].
• Modification of central nervous system effects of laudanosine by inhalation anaesthetics [13].
• However, laudanosine displayed an inhibitory effect at the low-affinity GABA receptors labeled by [3H]bicuculline methochloride, with an IC50 value of 10 microM [12].
• Atracurium was used to provide muscle relaxation; the level of neuromuscular block and plasma concentrations of atracurium and laudanosine were measured [14].

Anatomical context of NSC35045

• The authors hypothesized that laudanosine, a metabolite of atracurium and a central nervous system stimulant, might increase the minimum alveolar concentration (MAC) of halothane [15].
• We conclude that laudanosine crosses the blood-brain barrier and further study of its central nervous system effects in man is warranted [16].
• 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 [17].
• The transplacental transfer of laudanosine was low at 14 +/- 5%, with blood levels of 0.101 +/- 0.032 microM.L-1 in the umbilical vein [18].
• This compound was subsequently identified by mass spectral, gas chromatographic, and thin layer chromatographic tests as laudanosine, a metabolite of the skeletal muscle relaxant atracurium which was administered during emergency surgery [19].

Gene context of NSC35045

• The non-specific EEG/power spectra changes observed may reflect a direct CNS activity with neurodepression, since laudanosine was shown by its presence in CSF to cross the blood-brain barrier [5].
• We have investigated whether nitrous oxide antagonizes or augments the CNS stimulant action of laudanosine in mice by comparing the mean convulsive doses (CD50 (SE] of a control group and those following pretreatment with 65% nitrous oxide in oxygen for 20 and 180 min [20].
• Only glaucine and laudanosine inhibited K(+)-induced uterine contractions more than oxytocin-induced uterine contractions [21].

Analytical, diagnostic and therapeutic context of NSC35045

• Laudanosine (1 mg . kg-1 iv) was administered as a bolus, and its concentrations in plasma, CSF, urine, and bile were determined by liquid chromatography [8].
• An electroencephalogram (EEG) was done before the discontinuation of the infusion, and plasma concentrations of atracurium and laudanosine were measured at, and after, the termination of the atracurium infusion [1].
• Plasma concentrations of laudanosine, but not of atracurium, are increased during the anhepatic phase of orthotopic liver transplantation in pigs [22].
• Plasma laudanosine levels always remained well less that those associated with seizure activity in animal models [23].
• However, scoring the frequency of the spikes and bursts revealed no significant differences between the laudanosine and control groups [4].

References