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].

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> AChE

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： Cell Viability Assay[3] Cell Line: The human small cell lung carcinoma cell line NCI-H69 Concentration: 1 mM Incubation Time: Added every day for 2 days. Result: Markedly inhibited cell viability.

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.

MOLECULAR FORMULA :

C24-H34-N2-O4.2Br

MOLECULAR WEIGHT :

574.42

WISWESSER LINE NOTATION :

T6K DOTJ A1 A1 CQ CR DR D- CT6K DOTJ A1 A1 CQ &Q 2 &E

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

160 ug/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

EJPHAZ European Journal of Pharmacology. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1967- Volume(issue)/page/year: 33,145,1975

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

450 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

IRNEAE International Review of Neurobiology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 2,77,1960

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

46 ug/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

EJPHAZ European Journal of Pharmacology. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1967- Volume(issue)/page/year: 33,145,1975

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

150 ug/kg

TOXIC EFFECTS :

Tumorigenic - active as anti-cancer agent

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 152,253,1964

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

80 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 27,666,1974

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

15 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

IRNEAE International Review of Neurobiology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 2,77,1960

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

750 ug/kg

TOXIC EFFECTS :

Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

JMPCAS Journal of Medicinal and Pharmaceutical Chemistry. (Washington, DC) V.1-5, 1959-62. For publisher information, see JMCMAR. Volume(issue)/page/year: 4,505,1961

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

300 ug/kg

TOXIC EFFECTS :

Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

JMPCAS Journal of Medicinal and Pharmaceutical Chemistry. (Washington, DC) V.1-5, 1959-62. For publisher information, see JMCMAR. Volume(issue)/page/year: 4,505,1961

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

250 ug/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - tremor Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 119,20,1959

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

300 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

IRNEAE International Review of Neurobiology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 2,77,1960