{{Short description|Chemical compound}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 400103507 | IUPAC_name = (2''S'',2''S'')-2,2'-biphenyl-4,4'-diyl''bis''(2-hydroxy-4,4-dimethylmorpholin-4-ium) | image = Hemicholinium-3.svg | image_class = skin-invert-image | alt = Skeletal formula | width = 260 | image2 = Hemicholinium-3 cation spacefill.png | image_class2 = bg-transparent | alt2 = Space-filling model of the hemicholinium-3 cation
<!--Clinical data--> | tradename = | legal_status = | routes_of_administration =
<!--Pharmacokinetic data--> | bioavailability = | metabolism = | elimination_half-life = | excretion =
<!--Identifiers--> | IUPHAR_ligand = 4493 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 312-45-8 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 65NY3I7ZD0 | ATC_prefix = None | ATC_suffix = | PubChem = 9399 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 9029 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 268697
<!--Chemical data--> | C=24 | H=34 | N=2 | O=4 |charge=2+ | smiles = [Br-].[Br-].OC1(OCC[N+](C)(C)C1)c2ccc(cc2)c3ccc(cc3)C4(O)OCC[N+](C)(C)C4 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = OPYKHUMNFAMIBL-UHFFFAOYSA-L | synonyms = <small>2-[4-[4-(2-hydroxy-4,4-dimethylmorpholin-4-ium-2-yl)phenyl]phenyl]-4,4-dimethylmorpholin-4-ium-2-ol</small> }}
'''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.<ref name="Carlson">{{cite book | first= Neil R. | last= Carlson | name-list-style = vanc | year= 2007 | title= Physiology of Behavior | edition=9th | location= Boston | publisher=Pearson Education, Inc. | isbn= 978-0-205-46724-2 | page= 117}}</ref>
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.<ref>{{cite journal | vauthors = Freeman JJ, Kosh JW, Parrish JS | title = Peripheral toxicity of hemicholinium-3 in mice | journal = British Journal of Pharmacology | volume = 77 | issue = 2 | pages = 239–44 | date = October 1982 | pmid = 7139185 | pmc = 2044599 | doi = 10.1111/j.1476-5381.1982.tb09291.x }}</ref>
== See also == *Triethylcholine *Vesamicol
== References == {{Reflist}} {{Commons cat}} {{Acetylcholine metabolism and transport modulators}}
Category:Lactols Category:Morpholines Category:Quaternary ammonium compounds Category:Acetylcholine synthesis inhibitors Category:Biphenyls Category:Symmetrical biaryls