"目录号: HY-14316A
Membrane Transporter/Ion ChannelNeuronal Signaling-
Tebanicline hydrochloride (ABT594 hydrochloride) 是nAChR的调节物，具有有效的口服止痛活性。抑制cytisine与神经元nAChR的结合的Ki值为37 pM。
nAChR
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生物活性
Description
Tebanicline hydrochloride (ABT594 hydrochloride) is anAChRmodulator with potent, orally effective analgesic activity. It inhibits the binding of cytisine to α4β2 neuronal nAChRs with aKiof 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 Kiof 37 pM. Functionally, tebanicline is an agonist. At the transfected human α4β2 neuronal nAChR in K177 cells, with increased86Rb+efflux as a measure of cation efflux, ABT-594 has an EC50value of 140 nM with an intrinsic activitycompared with (?)-nicotine of 130%; at the nAChR subtype expressed in IMR-32 cells, an EC50of 340 nM; at the F11 dorsal root ganglion cell line, an EC50of 1220 nM; and via direct measurement of ion currents, an EC50value 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].
References
[1].Donnelly-Roberts DL, et al. ABT-594 [(R)-5-(2-azetidinylmethoxy)-2-chloropyridine]: a novel, orally effective analgesic acting via neuronal nicotinic acetylcholine receptors: I. In vitro characterization.J Pharmacol Exp Ther. 1998 May;285(2):777-86.
[2].Bannon AW, et al. ABT-594 [(R)-5-(2-azetidinylmethoxy)-2-chloropyridine]: a novel, orally effective antinociceptive agent acting via neuronal nicotinic acetylcholine receptors: II. In vivo characterization. J Pharmacol Exp Ther. 1998 May;285(2):787-94.
[3].Decker MW, et al. Antinociceptive effects of the novel neuronal nicotinic acetylcholine receptor agonist, ABT-594, in mice. Eur J Pharmacol. 1998 Apr 3;346(1):23-33.
[4].Decker MW, et al. The role of neuronal nicotinic acetylcholine receptors in antinociception: effects of ABT-594. J Physiol Paris. 1998 Jun-Aug;92(3-4):221-4.