Preclinical Pharmacology
Several publications describe the preclinical pharmacology of atracurium. Hughes and Payne described the preliminary pharmacology of atracurium in anesthethetized cats, dogs and rhesus monkeys. A 14C radiolabeled metabolism study in cats confirmed the lack of hepatic or renal involvement in the metabolism of atracurium: radioactivity eliminated in bile and urine was predominantly from metabolites rather than the unchanged parent drug.
Chapple and Clarke reported on the neuromuscular and cardiovascular effects of the breakdown products of atracurium and related substances in anesthetized cats. They concluded that the metabolites were of low potencies, and quite likely that the quantities present either as an impurity or formed after administration of therapeutic doses of atracurium (0.3–0.6 mg kg-1 i.v.) would be of no pharmacological importance. Laudanosine, the quaternary acid and metholaudanosine were devoid of neuromuscular blocking activity within the dose range 0.5–4 mg kg-1. However, within this dose range, they reported that the quaternary monoacrylate, the quaternary alcohol and the monoquaternary analogue produced a dose-dependent neuromuscular block. Administration of the quaternary monoacrylate, laudanosine, the quaternary alcohol, metholaudanosine and the monoquaternary analogue at 4 mg kg-1 doses resulted in a significant reduction in mean arterial pressure (by 30–70 mm Hg). Significant sympathetic blockade after preganglionic nerve stimulation was observed only with the monoquaternary analogue at a dose of 4 mg kg-1, whereas significant vagal blockade occurred after 4 mg kg-1 of the quaternary monoacrylate, the quaternary acid, the quaternary alcohol, and the monoquaternary analogue.
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