The purpose of this study was to explore the feasibility of utilizing the granatanol: N-methyl [9-azabicyclo (3.3.1) nonane] 3-alpha-ol as the terminal group in a series of new bisquaternary azabicycyclic diester-type neuromuscular blocking agents. Fifty two bisquaternary ammonium derivatives of several dicarboxylic acid esters of granatanol and three similar derivatives of pseudo granatanol have been investigated for neuromuscular blocking (NMB) potency (ED(50) s), onset and recovery of action and for cardiovascular side effects. All agents were studied first in anesthetized rats, and selected agents were subjected to further pharmacodynamic testing in rabbits, juvenile pigs, cats, dogs and monkeys. One agent was tested in continuous i.v. infusion mode in comparison with its corresponding tropine diester and the aminosteroid muscle relaxant, rocuronium. Several new and highly potent NMB granatanol derivatives are described, which are largely similar in NMB potency to the previously described tropine: N-methyl [8-azabicyclo (3.2.1)] 3-alpha-ol diester derivatives. The majority of the presently described granatanol derivatives displayed ultrashort onset and duration of actions. In that respect some of these agents proved to be the fastest and shortest acting non-depolarizing muscle relaxants described so far. On the negative side, many, but not all, granatanol derivatives produced cardiovascular side effects: e.g. changes in heart rate and blood pressure. Like with the similar tropinyl diester derivatives, cardiac vagal block was present with the majority of these agents as assessed in the rat, pig and cat. Few glutaryl, fumaryl and cyclobutane (trans) 1,2-dicarboxylyl granatanol diesters quaternized with disubstituted benzyl halides, bearing p-acyloxy radicals, showed excellent NMB profile. In these derivatives, however, the rapid decomposition of the p-acyloxy groups leads to formation of toxic quinone methene metabolites which precludes their further pharmaceutical development. The pseudo granatanol derivatives were less potent in the rat than the corresponding granatanols and were not further investigated. We conclude that the 9-azabicyclo (3.3.1) nonane (granatane) ring system can successfully replace the similar 8-azabicyclo (3.2.1) octane (tropane) ring system in building potent, utrashort acting NMB agents.