Linopirdine [DuP 996, 3, 3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one], a putative cognition enhancing drug, increases acetylcholine release in rat brain tissue and improves performance in animal models of learning and memory. Linopirdine was developed as a cognitive enhancing molecule and demonstrated to specifically block the potassium current generated by the brain specific KCNQ2-KCNQ3 proteins (M-channel). Linopirdine also acts as an agonist of TRPV1. At low concentrations linopirdine sensitizes both recombinant and native TRPV1 channels to heat, in a manner that is not prevented by the Kv7-channel opener flupirtine. Taken together, these results indicate that linopirdine exerts an excitatory action on mammalian nociceptors not only through inhibition of the M current but also through activation of the capsaicin receptor TRPV1. In the late 1980s, DuPont initiated clinical trials with linopirdine for Alzheimer’s disease. Linopirdine was regarded as a promising drug because it enhanced the release of acetylcholine in cholinergic nerve terminals in the brain only when its release was triggered and improved learning and memory in rodents and primates. Although clinical trials with linopirdine remained largely inconclusive or showed that it did not improve memory performance in elderly subjects, linopirdine became a valuable pharmacological tool. Development of Linopirdine for the treatment of Alzheimer's disease was discontinued.