ABT-594 is a potent agonist of neuronal α4β2 subunit-containing nicotinic acetylcholine receptors (nAChRs; Ki = 37 pM in a radioligand binding assay). It is selective for neuronal nAChRs over neuromuscular α1β1δγ subunit-containing nAChRs (Ki = 10,000 nM), α1B-, α2B-, and α2C- adrenergic receptors (Kis = 890, 597, and 342 nM, respectively), and 70 other receptors, enzymes, and transporters (Kis = >1,000 nM) in radioligand binding assays. ABT-594 induces [86Rb+] efflux in K177 cells transfected with human neuronal α4β2 subunit-containing nAChRs (EC50 = 140 nM). In vivo, ABT-594 (0.05 and 0.01 mg/kg, s.c.) increases latency to paw withdrawal in a hot-plate test in rats. It also induces hypothermia, seizures, and an increase in blood pressure.
