Hemicholinium 3

• CAT Number: I028681
• CAS Number: 312-45-8
• Molecular Formula: C24H34Br2N2O4
• Molecular Weight: 574.35
• Purity: ≥95%
• Synonyms: 2-[4-[4-(2-hydroxy-4,4-dimethylmorpholin-4-ium-2-yl)phenyl]phenyl]-4,4-dimethylmorpholin-4-ium-2-ol;dibromide
• InChI: InChI=1S/C24H34N2O4.2BrH/c1-25(2)13-15-29-23(27,17-25)21-9-5-19(6-10-21)20-7-11-22(12-8-20)24(28)18-26(3,4)14-16-30-24;;/h5-12,27-28H,13-18H2,1-4H3;2*1H/q+2;;/p-2
• InChIKey: OPYKHUMNFAMIBL-UHFFFAOYSA-L
• SMILES: C[N+]1(CCOC(C1)(C2=CC=C(C=C2)C3=CC=C(C=C3)C4(C[N+](CCO4)(C)C)O)O)C.[Br-].[Br-]

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

Reference

[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.
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[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.
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[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.
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[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.
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