Fig. 1. Representative force recordings of guinea pig tracheal ring preparations suspended in organ baths illustrating allosteric effects of rapacuronium (Rap). In A , rings were first precontracted twice with an increasing concentrations of acetylcholine, washed three times, and then exposed to 1–100 μm rapacuronium, resulting in an increase in force; after thorough washing (nine times), a repeat addition of 1–100 μm rapacuronium was without effect. ( B ) In the absence of acetylcholine precontraction, 1–100 μm rapacuronium was without effect; after thorough washing (nine times), an acetylcholine precontraction, and three washes, rapacuronium now increased force. ( C ) In the absence of acetylcholine precontraction, 1–100 μm rapacuronium was without effect; after thorough washing (nine times), a single 0.1-μm acetylcholine dose was added, and rapacuronium then resulted in increased force. These results illustrate that rapacuronium only increased baseline force in the presence of subthreshold concentrations of acetylcholine, consistent with a positive allosteric cooperativity with acetylcholine at the M3 muscarinic receptor. Illustrations are typical of at least five independent experiments for each condition.