tcsc6400 Tebanicline (hydrochloride)

Tebanicline hydrochloride (ABT594 hydrochloride) is a nAChR modulator with potent, orally effective analgesic activity. It inhibits the binding of cytisine to α4β2 neuronal nAChRs with a K_i of 37 pM.

IC50 & Target: Ki: 37 pM (nAChR)^[1]

In Vitro: Tebanicline is a novel, potent cholinergic nAChR ligand with analgesic properties that shows preferential selectivity for neuronal nAChRs. It inhibits the binding of cytisine to α4β2 neuronal nAChRs with a K_i of 37 pM. Functionally, tebanicline is an agonist. At the transfected human α4β2 neuronal nAChR in K177 cells, with increased ⁸⁶Rb⁺ efflux as a measure of cation efflux, ABT-594 has an EC₅₀ value of 140 nM with an intrinsic activitycompared with (−)-nicotine of 130%; at the nAChR subtype expressed in IMR-32 cells, an EC₅₀ of 340 nM; at the F11 dorsal root ganglion cell line, an EC₅₀ of 1220 nM; and via direct measurement of ion currents, an EC₅₀ value of 56,000 nM at the human α7 homo-oligimeric nAChR produced in oocytes^[1]

In Vivo: Tebanicline is a potent antinociceptive agent with full efficacy in models of acute and persistent pain and that these effects are mediated predominately by an action at central neuronal nAChRs^[2]. Tebanicline produces significant antinociceptive effects in mice against both acute noxious thermal stimulation. ABT-594 is orally active, but 10-fold less potent by this route than after i.p. administration. The antinociceptive effect of ABT-594 is prevented, but not reversed, by the noncompetitive neuronal nicotinic acetylcholine receptor antagonist^[3]. Tebanicline has antinociceptive effects in rat models of acute thermal, persistent chemical, and neuropathic pain. Direct injection of tebanicline into the nucleus raphe magnus (NRM) is antinociceptive in a thermal threshold test and destruction of serotonergic neurons in the NRM attenuates the effect of systemic tebanicline^[4].