Many synthetic compounds to which we attribute specific activities are produced as racemic mixtures of stereoisomers, and it may be that all of the desired activity comes from a single enantiomer. We have previously shown this to be the case with the a7 nicotinic acetylcholine receptor positive allosteric modulator (PAM) TQS, and the a7 ago-PAM 4BP-TQS. 2,3,5,6TMP-TQS, previously published as a "silent allosteric modulator" and an antagonist of a7 allosteric activation, shares the same scaffold with three chiral centers as the aforementioned compounds. We isolated the enantiomers of 2,3,5,6TMP-TQS and determined that the (-) isomer was a significantly better antagonist than the (+) isomer of the allosteric activation of both wild-type a7 and the non-orthosterically activatible C190A a7 mutant by the ago-PAM GAT107 (the active isomer of 4BP-TQS). In contrast (+)2,3,5,6TMP-TQS proved to be an a7 PAM. (-)2,3,5,6TMP-TQS was shown to antagonize the allosteric activation of a7 by the structurally unrelated ago-PAM B-973B as well as the allosteric activation of the TQS-sensitive a4b2L15'M mutant. In silico docking of 2,3,5,6TMP-TQS in the putative allosteric activation binding site suggested a specific interaction of the (-) enantiomer with a7T106, and allosteric activation of a7T106 mutants was not inhibited by (-)2,3,5,6TMP-TQS, confirming the importance of this interaction and supporting the model of the allosteric binding site. Comparisons and contrasts between 2,3,5,6TMP-TQS isomers and active and inactive enantiomers of other TQS-related compounds identify the orientation of the cyclopentenyl ring to the plane of the core quinoline to be a crucial determinate of PAM activity.