CAS 312-45-8|Hemicholinium 3

Introduction：Basic information about CAS 312-45-8|Hemicholinium 3, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Hemicholinium 3 BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Articles40
7. Synonyms

Common Name	Hemicholinium 3
CAS Number	312-45-8	Molecular Weight	574.35
Density	/	Boiling Point	/
Molecular Formula	C₂₄H₃₄Br₂N₂O₄	Melting Point	180 °C
MSDS	ChineseUSA	Flash Point	/
Symbol	GHS06	Signal Word	Danger

Names

Name	2-[4-[4-(2-hydroxy-4,4-dimethylmorpholin-4-ium-2-yl)phenyl]phenyl]-4,4-dimethylmorpholin-4-ium-2-ol,dibromide
Synonym	More Synonyms

Hemicholinium 3 BiologicalActivity

Description	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].
Related Catalog	Research Areas >>Neurological DiseaseSignaling Pathways >>Neuronal Signaling >>AChE
In Vitro	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.
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].
References	[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.

Chemical & Physical Properties

Melting Point	180 °C
Molecular Formula	C₂₄H₃₄Br₂N₂O₄
Molecular Weight	574.35
Exact Mass	572.08900
PSA	58.92000
InChIKey	OPYKHUMNFAMIBL-UHFFFAOYSA-L
SMILES	C[N+]1(C)CCOC(O)(c2ccc(-c3ccc(C4(O)C[N+](C)(C)CCO4)cc3)cc2)C1.[Br-].[Br-]

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QF2450000

CHEMICAL NAME :: Morpholinium, 2,2'-(4,4'-biphenylylene)bis(2-hydroxy-4,4-dimethyl-, dibromide

CAS REGISTRY NUMBER :: 312-45-8

LAST UPDATED :: 199701

DATA ITEMS CITED :: 11

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

Safety Information

Symbol	GHS06
Signal Word	Danger
Hazard Statements	H301 + H311 + H331-H315-H319-H335
Precautionary Statements	P261-P280-P301 + P310-P305 + P351 + P338-P311
Personal Protective Equipment	Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges
Hazard Codes	T: Toxic;
Risk Phrases	23/24/25-36/37/38
Safety Phrases	S26;S45;S36/S37/S39
RIDADR	UN 2811 6.1/PG 2
RTECS	QF2450000
Packaging Group	III
Hazard Class	6.1(b)

Articles40

Identification and characterization of ML352: a novel, noncompetitive inhibitor of the presynaptic choline transporter.

ACS Chem. Neurosci. 6(3) , 417-27, (2015)

The high-affinity choline transporter (CHT) is the rate-limiting determinant of acetylcholine (ACh) synthesis, yet the transporter remains a largely undeveloped target for the detection and manipulati...

Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries.

J. Pharmacol. Exp. Ther. 354 , 121-30, (2015)

Mild hypothermia causes endothelium-dependent relaxations, which are reduced by the muscarinic receptor antagonist atropine. The present study investigated whether endothelial endogenous acetylcholine...

Four cation-selective transporters contribute to apical uptake and accumulation of metformin in Caco-2 cell monolayers.

J. Pharmacol. Exp. Ther. 352(3) , 519-28, (2015)

Metformin is the frontline therapy for type II diabetes mellitus. The oral bioavailability of metformin is unexpectedly high, between 40 and 60%, given its hydrophilicity and positive charge at all ph...

Synonyms

Hemicholinium dibromide

HC-3

HEMICHOLINIUM 3

EINECS 206-227-3

Hemicholinium 3 dibromide

Hemicholinium bromide

Hemicholinium-3 bromide

Hemicholinium-3

MFCD00011978

hemicholinium

Hemicholine

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