Cipralisant

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Cipralisant

Systematic (IUPAC) name
(1S,2S)-4-(2-(5,5-dimethylhex-1-ynyl) cyclopropyl)imidazole
Clinical data
Legal status	?
Identifiers

ATC code	None
PubChem	CID 10512919
ChemSpider	8688320^N
UNII	309713XSKW^N
ChEMBL	CHEMBL278462^N
Chemical data
Formula	C₁₄H₂₀N₂
Mol. mass	216.32 g/mol
SMILES C(#CCCC(C)(C)C)[C@H]2C[C@@H]2c1cncn1
InChI InChI=1S/C14H20N2/c1-14(2,3)7-5-4-6-11-8-12(11)13-9-15-10-16-13/h9-12H,5,7-8H2,1-3H3,(H,15,16)/t11-,12-/m0/s1^N Key:CVKJAXCQPFOAIN-RYUDHWBXSA-N^N
N (what is this?) (verify)

Cipralisant (GT-2331, tentative trade name Perceptin) is an extremely potent Histamine H₃ receptor ligand originally developed by Gliatech.^[1] Cipralisant was initially classified as a selective H₃ antagonist, and seemed to be well tolerated during early testing, entering Phase II trials for ADHD in 2000. It has now been found to actually be an H3 agonist.

The relatively recent cloning of human H₃ receptor, as well as the discovery of its constitutive activity provided the ability to better assess the activity of H₃ receptor ligands. Consequently cipralisant was reassessed as an H₃ receptor agonist in human and rat recombinant systems, showing functional selectivity and stimulating one type of G-protein coupled pathway while failing to activate other intracellular pathways.^[2]

Gliatech filed for bankruptcy in 2002, and its intellectual property was inherited by Merck. The development of cipralisant seems to have been suspended since 2003 but research is ongoing, and recently it has been shown that it is the 1S,2S enantiomer which is the biologically active one.^[3]

References

↑ Detailed pharmacological characterization of GT-2331 for the rat histamine H3 receptor
↑ Krueger, KM; Witte, DG; Ireland-Denny, L; Miller, TR; Baranowski, JL; Buckner, S; Milicic, I; Esbenshade, TA; Hancock, AA (2005). "G protein-dependent pharmacology of histamine H3 receptor ligands: evidence for heterogeneous active state receptor conformations". The Journal of Pharmacology and Experimental Therapeutics 314 (1): 271–81. doi:10.1124/jpet.104.078865. PMID 15821027.
↑ An Efficient Multigram Synthesis of the Potent Histamine H3 Antagonist GT-2331 and the Reassessment of the Absolute Configuration

Histaminergics

Receptor

H₁	Agonists: 2-Pyridylethylamine Betahistine Histamine HTMT UR-AK49 Antagonists: 1st generation: 4-Methyldiphenhydramine Alimemazine Antazoline Azatadine Bamipine Benzatropine/Benztropine Bepotastine Bromazine Brompheniramine Buclizine Captodiame Carbinoxamine Chlorcyclizine Chloropyramine Chlorothen Chlorphenamine Chlorphenoxamine Cinnarizine Clemastine Clobenzepam Clocinizine Cyclizine Cyproheptadine Dacemazine Deptropine Dexbrompheniramine Dexchlorpheniramine Dimenhydrinate Dimetindene Diphenhydramine Diphenylpyraline Doxylamine Embramine Etodroxizine Etybenzatropine/Ethylbenztropine Etymemazine Flunarizine Histapyrrodine Homochlorcyclizine Hydroxyethylpromethazine Hydroxyzine Isopromethazine Isothipendyl Meclozine Mepyramine/Pyrilamine Mequitazine Methafurylene Methapyrilene Methdilazine Moxastine Niaprazine Orphenadrine Oxatomide Oxomemazine Phenindamine Pheniramine Phenyltoloxamine Pimethixene Piperoxan Pipoxizine Promethazine Propiomazine Pyrrobutamine Talastine Thenalidine Thenyldiamine Thiazinamium Thonzylamine Tolpropamine Tripelennamine Triprolidine 2nd generation: Acrivastine Alinastine Astemizole Azelastine Bamirastine Barmastine Bepiastine Bepotastine Bilastine Cabastinen Carebastine Cetirizine Clemastine Clemizole Clobenztropine Dorastine Ebastine Emedastine Epinastine Flezelastine Ketotifen Latrepirdine Levocabastine Linetastine Loratadine Mapinastine Mebhydrolin Mizolastine Moxastine Noberastine Octastine Olopatadine Perastine Piclopastine Rocastine Rupatadine Setastine Talastine Temelastine Terfenadine Zepastine 3rd generation: Desloratadine Fexofenadine Levocetirizine Ungrouped: Belarizine Efletirizine Elbanizine Flotrenizine Medrylamine Napactadine Pibaxizine Tagorizine Trelnarizine Trenizine Vapitadine Miscellaneous: Tricyclic antidepressants (amitriptyline, doxepin, trimipramine, etc) Tetracyclic antidepressants (mianserin, mirtazapine, etc) Typical antipsychotics (chlorpromazine, thioridazine, etc) Atypical antipsychotics (clozapine, olanzapine, quetiapine, etc)

H₂	Agonists: Amthamine Betazole Dimaprit Histamine HTMT Impromidine UR-AK49 Antagonists: Bisfentidine Burimamide Cimetidine Dalcotidine Donetidine Ebrotidine Etintidine Famotidine Lafutidine Lamtidine Lavoltidine/Loxtidine Lupitidine Metiamide Mifentidine Niperotidine Nizatidine Osutidine Oxmetidine Pibutidine Quisultazine/Quisultidine Ramixotidine Ranitidine Roxatidine Sufotidine Tiotidine Tuvatidine Venritidine Xaltidine

H₃	Agonists: α-Methylhistamine Cipralisant Histamine Imetit Immepip Immethridine Methimepip Proxyfan Antagonists: A-349,821 A-423,579 ABT-239 Betahistine Burimamide Ciproxifan Clobenpropit Conessine GSK-189,254 Impentamine Iodophenpropit JNJ-5,207,852 MK-0249 NNC-38-1,049 PF-03654746 Pitolisant SCH-79,687 Thioperamide VUF-5,681

H₄	Agonists: 4-Methylhistamine Histamine VUF-8,430 Antagonists: JNJ-7,777,120 Thioperamide VUF-6,002

Transporter

VMAT	Inhibitors: Ibogaine Reserpine Tetrabenazine

Enzyme

HDC	Inhibitors: Catechin Meciadanol Naringenin Tritoqualine

HNMT	Inhibitors: Amodiaquine Diphenhydramine Harmaline Metoprine Quinacrine SKF-91,488 Tacrine

DAO	Inhibitors: Aminoguanidine

Others

Endogenous	Histamine; Precursors: L-Histidine; Cofactors: Vitamin B6

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