Acetylcholinesterase (AChE) inhibited by the organophosphate soman (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex. This reaction is called aging. The effect of the four mono- and bisquaternary ammonium compounds tetramethylammonium (TMA), hexamethonium, decamethonium and suxamethonium on the reactivatability of soman-inhibited, solubilized AChE from human erythrocytes was investigated in vitro. All compounds were reversible inhibitors of AChE; the respective dissociation constants and the type of inhibition exhibited considerable differences. The affinities to both the active and the allosteric site were considerably higher for suxamethonium (Kii 81.3 microM; Ki 15.9 microM) and decamethonium (Kii 15.4 microM; Ki 4.4 microM) than for TMA (Kii 1 mM; Ki 289.6 microM) and hexamethonium (Kii 4.5 mM; Ki 331.8 microM). The reactivation experiments were performed in a four-step procedure (soman-inhibition at 0 degree and pH 10, aging at 37 degrees and pH 7.3, reactivation by the oxime HI 6 at 37 degrees and pH 7.3 followed by AChE assay). After these four steps (total duration 55 min), AChE was inhibited by soman to 95-100%. HI 6 could reactivate about 20% of the inhibited enzyme. All effectors increased the AChE reactivatability by HI 6 when added before aging was started. The maximal increase in reactivatability was higher in the presence of 1.6 mM suxamethonium (+35.8%) and 150 microM decamethonium (+40%) than of 22 mM TMA (+22.5%) and 8.3 mM hexamethonium (+19.2%). If the effectors were added after 5 min of aging they increased the activity of soman-inhibited AChE, but to a considerably smaller extent than HI 6. A good correlation of the respective Kii values and the effective concentrations of these drugs was observed, indicating that an allosteric binding site of AChE might be involved in the protective effect of these drugs.