Pharmacological action of breakdown products of atracurium and related substances.

The neuromuscular and cardiovascular effects of the breakdown products of atracurium and related substances have been studied in cats anaesthetized with chloralose. Laudanosine, the quaternary acid and metholaudanosine had no neuromuscular blocking activity within the dose range 0.5-4 mg kg-1. However, the quaternary monoacrylate, the quaternary alcohol and the monoquaternary analogue produced a dose-dependent neuromuscular block within this dose range. At 4 mg kg-1 mean arterial pressure was significantly reduced by 30-70 mm Hg following the administration of the quaternary monoacrylate, laudanosine, the quaternary alcohol, metholaudanosine and the monoquaternary analogue. At this dose only the monoquaternary analogue caused significant sympathetic blockade after preganglionic nerve stimulation. Significant vagal blockade occurred after 4 mg kg-1 of the quaternary monoacrylate, the quaternary acid, the quaternary alcohol and the monoquaternary analogue. In view of the low potencies of these substances, it is likely that the quantities present either as an impurity or likely to be formed after administration of therapeutic doses of atracurium (0.3-0.6 mg kg-1 i.v.) are of no pharmacological importance.