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  • Title: Neuromuscular pharmacology of TAAC3, a new nondepolarizing muscle relaxant with rapid onset and ultrashort duration of action.
    Author: Gyermek L, Lee C, Cho YM, Nguyen N, Tsai SK.
    Journal: Anesth Analg; 2002 Apr; 94(4):879-85, table of contents. PubMed ID: 11916790.
    Abstract:
    UNLABELLED: We selected bis [N-(3,4-diacetoxybenzyl) tropanium-3alpha-yl] glutarate dibromide (TAAC3) from many new tropinyl diester derivatives to evaluate its neuromuscular blocking (NMB) and autonomic side effects on anesthetized rats, rabbits, guinea pigs, cats, pigs, dogs, and monkeys. NMB potency, onset, recovery index, and duration of action were determined. Comparisons of these pharmacologic variables were made between TAAC3 and rocuronium. In the cat, the degrees of train-of-four and tetanic fade, posttetanic potentiation, and pharmacologic antagonism were evaluated. For determination of the NMB maintenance dose, TAAC3 was also given to rabbits and pigs in the initial dose/maintenance infusion mode. Cardiac vagal block was evaluated in the rat, pig, cat, and guinea pig on the basis of the inhibition of the bradycardia to stimulation of the vagus nerve. Sympathetic ganglion block was studied on the superior cervical ganglion-nictitating membrane preparation of the cat. TAAC3 produced nondepolarizing NMB. Its NMB 90% effective doses ranged from 90 to 425 microg/kg, depending on the species. TAAC3 had a faster onset (0.8-1.0 min), shorter recovery index (0.6-1.1 min), and shorter duration of action (1.8-3.5 min) than rocuronium. It produced a slight cumulative effect on infusion, but not on repeated single-dose administration. Cardiac vagal block was present at doses exceeding the NMB 90% effective dose. In the cat and pig at equipotent NMB doses, the degree of cardiac vagal block was similar to that of rocuronium. There was no demonstrable sympathetic ganglion block in the cat. In view of its favorable NMB characteristics, TAAC3 is now undergoing detailed preclinical studies. IMPLICATIONS: We developed a new nondepolarizing muscle relaxant, TAAC3, and investigated it in several animal models. TAAC3 has shown a very rapid onset and an ultrashort duration of neuromuscular blocking action. A minor degree of cardiac vagal block was observed. TAAC3 is promising for further studies.
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