Hemicholinium-3

Hemicholinium-3
Clinical data


Synonyms	2-[4-[4-(2-hydroxy-4,4-dimethylmorpholin-4-ium-2-yl)phenyl]phenyl]-4,4-dimethylmorpholin-4-ium-2-ol
ATC code	None
Identifiers
IUPAC name (2S,2S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium)
CAS Number	312-45-8^Y
PubChem CID	9399
IUPHAR/BPS	4493
ChemSpider	9029^Y
ChEMBL	CHEMBL268697^N
ECHA InfoCard	100.005.663
Chemical and physical data
Formula	C₂₄H₃₄N₂O₄²⁺
Molar mass	414.538 g/mol
3D model (JSmol)	Interactive image
SMILES [Br-].[Br-].OC1(OCC[N+](C)(C)C1)c2ccc(cc2)c3ccc(cc3)C4(O)OCC[N+](C)(C)C4
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^Y Key:OPYKHUMNFAMIBL-UHFFFAOYSA-L^Y
^NY (what is this?) (verify)

Hemicholinium-3 (HC3), also known as hemicholine, is a drug which blocks the reuptake of choline by the high-affinity choline transporter (ChT; encoded in humans by the gene SLC5A7) at the presynapse. The reuptake of choline is the rate limiting step in the synthesis of acetylcholine; hence, hemicholinium-3 decreases the synthesis of acetylcholine. It is therefore classified as an indirect acetylcholine antagonist.^[1]

Acetylcholine is synthesized from choline and a donated acetyl group from acetyl-CoA, by the action of choline acetyltransferase (ChAT). Thus, decreasing the amount of choline available to a neuron will decrease the amount of acetylcholine produced. Neurons affected by hemicholinium-3 must rely on the transport of choline from the soma (cell body), rather than relying on reuptake of choline from the synaptic cleft.

Toxicity

Hemicholinium-3 is highly toxic because it interferes with cholinergic neurotransmission. The LD50 of hemicholinium-3 for mice is about 35 μg.^[2]

References

↑ Carlson, Neil R. (2007). Physiology of Behavior (9th ed.). Boston: Pearson Education, Inc. p. 117. ISBN 0-205-46724-5.
↑ Freeman, JJ; Kosh, JW; Parrish, JS (October 1982). "Peripheral toxicity of hemicholinium-3 in mice". British Journal of Pharmacology. 77 (2): 239–44. PMC 2044599. PMID 7139185.

Acetylcholine metabolism and transport modulators

Enzyme
(modulators)

ChAT	Inhibitors: 1-(-Benzoylethyl)pyridinium 2-(α-Naphthoyl)ethyltrimethylammonium 3-Chloro-4-stillbazole 4-(1-Naphthylvinyl)pyridine Acetylseco hemicholinium-3 Acryloylcholine AF64A B115 BETA CM-54,903 N,N-Dimethylaminoethylacrylate N,N-Dimethylaminoethylchloroacetate
AChE	Inhibitors: Reversible: Carbamates: Aldicarb Aminocarb Bendiocarb Bufencarb Carbaryl Carbendazim Carbetamide Carbofuran Carbosulfan Chlorbufam Chloropropham Dimetilan Ethienocarb Ethiofencarb Fenobucarb Formetanate Formparanate Methiocarb Methomyl Metolcarb Miotine Oxamyl Phenmedipham Pinmicarb Pirimicarb Propamocarb Propham Propoxur Thiofanox; Stigmines: Distigmine Eptastigmine Ganstigmine Neostigmine Phenserine Physostigmine Pyridostigmine Quilostigmine Rivastigmine Terestigmine; Others: Acotiamide Ambenonium Caffeine Donepezil EA-3990 EA-4056 Edrophonium Galantamine Huperzine A Ipidacrine Itopride Ladostigil Minaprine Octamethylene-bis(5-dimethylcarbamoxyisoquinolinium bromide) T-1123 Tacrine Zanapezil Irreversible: Organophosphates: Acephate Anatoxin-a(S) Azinphos-ethyl Azinphos-methyl BAY-29952 Bensulide Cadusafos Carbophenothion Chlorethoxyfos Chlorfenvinphos Chlorpyrifos Chlorpyrifos-methyl Coumaphos Cyanophos Cyclosarin Demephion Demeton Demeton-S-methyl Dialifor Diazinon Dichlorvos Dicrotophos Diisopropyl fluorophosphate Diisopropylphosphate Dimefox Dimethoate Dimethyl 4-(methylthio)phenyl phosphate Dioxathion Disulfoton EA-2192 EA-3148 Echothiophate Endothion Ethion Ethoprop Fenamiphos Fenitrothion Fenthion Fluorotabun Fonofos Formothion Fosthiazate GV Hexaethyl tetraphosphate Isofluorophate Isoxathion Leptophos Malaoxon Malathion Methamidophos Methidathion Methyl phenkapton Metrifonate Mevinphos Monocrotophos Naled Novichok agent Omethoate Oxydemeton-methyl Paraoxon Parathion Parathion-methyl Phorate Phosalone Phosfolan Phosmet Phosphamidon Phoxim Pirimiphos-methyl Profenofos Prothoate Sarin Soman Tabun Tebupirimfos Temefos Terbufos Tetrachlorvinphos Tetraethyl pyrophosphate Triazofos Tribufos Trichlorfon Trichloronate Tricresyl phosphate VE VG VM VP VS VR VX; Others: Demecarium Fasciculins (green mamba toxins) (1, 2, 3, 4) Onchidal (Onchidella binneyi) Methanesulfonyl fluoride Unsorted: α-Pinene α-Viniferin Affinine Affinisine Arisugacin A Bulbocapnine Conodurine Coronaridine Corydaline Corynoline Crimidine Cyclanoline Cymserine Harmaline Kobophenol A Lactucopicrin Lycorine Phosacetim Rosmarinic acid Stercuronium iodide Taspine Tetrahydrocannabinol Ungeremine Ungiminorine Dimethylcarbamoyl fluoride Reactivators: Asoxime chloride Methoxime Obidoxime Pralidoxime Trimedoxime bromide
BChE	Inhibitors: Affinine Affinisine Conodurine Cymserine Ladostigil Profenamine (ethopropazine) Rivastigmine Tacrine ZINC-12613047 Many of the other AChE inhibitors listed above

Transporter
(modulators)

CHT	Inhibitors: Hemicholinium-3 (hemicholine) Triethylcholine Enhancers: Coluracetam
VAChT	Inhibitors: Vesamicol

Release
(modulators)

Inhibitors	SNAP-25 inactivators: Botulinum toxin (A, C, E) VAMP inactivators: Botulinum toxin (B, D, F, G) Others: Bungarotoxins (β-bungarotoxin, γ-bungarotoxin)
Enhancers	LPHN agonists: α-Latrotoxin Others: Atracotoxin (e.g., robustoxin, versutoxin) Crotoxin

See also: Receptor/signaling modulators • Muscarinic acetylcholine receptor modulators • Nicotinic acetylcholine receptor modulators

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