Hemicholinium 3

Hemicholinium 3 is a competitive inhibitor of the high affinity choline transporter (HACU) with a Ki value of 25 nM. Hemicholinium 3, a neuromuscular blocking agent which inhibits the synthesis and the release of acetylcholine (ACh)[1]. Hemicholinium 3 inhibits the Epibatidine-evoked contraction and [3H]acetylcholine release with IC50s of 897 nM and 693 nM, respectively[2].

Hemicholinium 3 (HC-3) inhibits the presynaptic nicotinic acetylcholine receptors of myenteric neurons. HC-3 inhibits nAChRs located on the terminal region of myenteric neurons of guinea-pig longitudinal muscle strip preparation[2]. Hemicholinium 3 (HC-3) inhibits[3H]choline uptake with the Ki value of 13.3 μM in NCI-H69 cells[3].HC-3 (1 mM) significantly inhibits cell viability and increases caspase-3/7 activity in NCI-H69 cells[3]. Hemicholinium 3 (Hemicholinium-3) inhibits sodium dependent high affinity choline uptake (IC50=18 nM)[4]. In vivo:

Hemicholinium-3 impairs spatial learning. HC-3 (2.5, 5.0 μg/rat/ICV; 1 h before training) dose dependently impairs spatial learning[5].

[1]. PATRICE GUYENET, et al. Inhibition by Hemicholinium-3 of [14C] Acetylcholine Synthesis and [3H] Choline High-Affinity Uptake in Rat Striatal Synaptosomes.Molecular Pharmacology September 1973, 9 (5) 630-639.
[2]. PÉter Mandl, et al. Inhibitory effect of hemicholinium-3 on presynaptic nicotinic acetylcholine receptors located on the terminal region of myenteric motoneurons. Neurochem Int. 2006 Sep;49(4):327-33.
[3]. Masato Inazu, et al. Functional expression of choline transporter-like protein 1 (CTL1) in small cell lung carcinoma cells: a target molecule for lung cancer therapy. Pharmacol Res. 2013 Oct;76:119-31.
[4]. T K Chatterjee, et al. Methylpiperidine analog of hemicholinium-3: a selective, high affinity non-competitive inhibitor of sodium dependent choline uptake system. Eur J Pharmacol. 1988 May 10;149(3):241-8.
[5]. J J Hagan, et al. Hemicholinium-3 impairs spatial learning and the deficit is reversed by cholinomimetics. Psychopharmacology (Berl). 1989;98(3):347-56.