THIOPERAMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H24N4S
Molecular Weight	292.4445
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1CCC(CC1)N=C(N2CCC(CC2)c3cnc[nH]3)S

InChI

InChIKey=QKDDJDBFONZGBW-UHFFFAOYSA-N

InChI=1S/C15H24N4S/c20-15(18-13-4-2-1-3-5-13)19-8-6-12(7-9-19)14-10-16-11-17-14/h10-13H,1-9H2,(H,16,17)(H,18,20)

HIDE SMILES / InChI

Molecular Formula	C15H24N4S
Molecular Weight	292.4445
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800004362
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22918191 | https://www.ncbi.nlm.nih.gov/pubmed/16432504

Thioperamide is an antihistamine at H3 and H4 receptors. Thioperamide behaves as both antagonist and inverse agonist.Thioperamide is under preclinical development with Glaxo Wellcome (UK) for the treatment of short-term memory impairment. It has also demonstrated antiarrhythmic effects in preclinical trials. Active development of thioperamide appears to have been discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H3 receptor 38 Target ID: CHEMBL264 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22918191 \| https://www.ncbi.nlm.nih.gov/pubmed/15341517 \| https://www.ncbi.nlm.nih.gov/pubmed/8864541	Antagonist 2575		1.1 nM [Ki]
Histamine H4 receptor 17 Target ID: CHEMBL3759 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22918191 \| https://www.ncbi.nlm.nih.gov/pubmed/11561071	Antagonist 2575		27.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cognition disorders 17 Sources: http://adisinsight.springer.com/drugs/800004362	Primary		Preclinical	Unknown Approved Use Unknown
Arrhythmia 37 Sources: http://adisinsight.springer.com/drugs/800004362	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Muscarinic, adenosine A(2) and histamine H(3) receptor modulation of haloperidol-induced c-fos expression in the striatum and nucleus accumbens.	2002	12044460
Characterisation of the calcium responses to histamine in capsaicin-sensitive and capsaicin-insensitive sensory neurones.	2002	11958874
Contractile response of horse deep dorsal penile vein to histamine.	2002 Apr	11979322
Effects of histidine, a precursor of histamine, on pentylenetetrazole-induced seizures in rats.	2002 Apr	11931695
Putative effect of Helicobacter pylori and gastritis on gastric acid secretion in cat.	2002 Apr	11897633
Behavioral characterization of mice lacking histamine H(3) receptors.	2002 Aug	12130692
Targeted disruption of H3 receptors results in changes in brain histamine tone leading to an obese phenotype.	2002 Dec	12488429
Identification of a histamine H4 receptor on human eosinophils--role in eosinophil chemotaxis.	2002 Feb-Nov	12503632
Histamine H3-receptor blockade in the rat nucleus basalis magnocellularis improves place recognition memory.	2002 Jan	11862340
Different role of the histamine H3-receptor in vagal-, betanechol-, pentagastrin-induced gastric acid secretion in anaesthetized rats.	2002 Jul	12190086
Rodent antinociception following acute treatment with different histamine receptor agonists and antagonists.	2002 Jun	12175473
Differential in vivo effects of H3 receptor ligands in a new mouse dipsogenia model.	2002 Jun	12175472
Modulation of the discriminative stimulus effects of cocaine and methamphetamine by the histaminergic system.	2002 Jun	12166087
Histamine H(2) -like receptors in chick cerebral cortex: effects on cyclic AMP synthesis and characterization by [(3) H]tiotidine binding.	2002 Jun	12065605
Effects of N-alpha-methyl-histamine on human H(2) receptors expressed in CHO cells.	2002 Jun	12010879
Betahistine dihydrochloride interaction with the histaminergic system in the cat: neurochemical and molecular mechanisms.	2002 Jun 20	12098586
Endogenous histamine in the medial septum-diagonal band complex increases the release of acetylcholine from the hippocampus: a dual-probe microdialysis study in the freely moving rat.	2002 May	12059975
Role of histamine H3 receptors in control of mouse intestinal motility in vivo and in vitro: comparison with alpha2-adrenoceptors.	2002 May	12018901
Experimental anxiety induced by histaminergics in mast cell-deficient and congenitally normal mice.	2002 May	11900817
Influence of SKF 91488, histamine N-methyltransferase inhibitor, on the central cardiovascular regulation during controlled, stepwise hemorrhagic hypotension in rats.	2002 May-Jun	12398155
Endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats--studies with histamine N-methyltransferase inhibitor SKF 91488.	2002 Nov	12540019
Activation of the extraneuronal monoamine transporter (EMT) from rat expressed in 293 cells.	2002 Nov	12411423
Coordination of histamine H3 receptor antagonists with human adrenal cytochrome P450 enzymes.	2002 Nov	12372902
Histamine h(4) and h(2) receptors control histamine-induced interleukin-16 release from human CD8(+) T cells.	2002 Oct	12235264
Histamine H3 receptor activation inhibits neurogenic sympathetic vasoconstriction in porcine nasal mucosa.	2002 Oct 11	12359275
Characteristics of recombinantly expressed rat and human histamine H3 receptors.	2002 Oct 18	12393057
High-frequency oscillation in the hippocampus of the behaving rat and its modulation by the histaminergic system.	2003	12699334
Critical role of histamine H4 receptor in leukotriene B4 production and mast cell-dependent neutrophil recruitment induced by zymosan in vivo.	2003 Dec	14551291
Histamine-induced chloride secretion is mediated via H2-receptors in the pig proximal colon.	2003 Feb	12665126
Histaminergic modulation of the intact respiratory network of adult mice.	2003 Feb	12634928
Histamine inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production in an intercellular adhesion molecule-1- and B7.1-dependent manner.	2003 Feb	12538815
Replacement of imidazole by a piperidine moiety differentially affects the potency of histamine H3-receptor antagonists.	2003 Jan	12616340
Functional identification of epithelial and smooth muscle histamine-dependent relaxing mechanisms in the bovine trachea, but not in bronchi.	2003 Jan	12524021
Neuroimmune interactions in guinea pig stomach and small intestine.	2003 Jan	12388180
Central endogenous histamine modulates sympathetic outflow through H3 receptors in the conscious rabbit.	2003 Jul	12839877
H3 receptor blockade by thioperamide enhances cognition in rats without inducing locomotor sensitization.	2003 Jun	12682709
Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells.	2003 Jun	12626656
Two novel and selective nonimidazole histamine H3 receptor antagonists A-304121 and A-317920: I. In vitro pharmacological effects.	2003 Jun	12606603
Two novel and selective nonimidazole H3 receptor antagonists A-304121 and A-317920: II. In vivo behavioral and neurophysiological characterization.	2003 Jun	12606600
Antinociceptive mechanisms of orally administered decursinol in the mouse.	2003 Jun 13	12759141
Activation of spinal histamine H3 receptors inhibits mechanical nociception.	2003 Jun 6	12798951
Regulation by prostaglandin E2 and histamine of angiogenesis in inflammatory granulation tissue.	2003 May	12772586
Possible role of L-carnosine in the regulation of blood glucose through controlling autonomic nerves.	2003 Nov	14610252
Histamine induces cytoskeletal changes in human eosinophils via the H(4) receptor.	2003 Nov	14530216
Generation and characterization of highly constitutive active histamine H3 receptors.	2003 Oct	12954820
Aminergic control of high-frequency (approximately 200 Hz) network oscillations in the hippocampus of the behaving rat.	2003 Sep 11	12902028
Critical role of L-selectin and histamine H4 receptor in zymosan-induced neutrophil recruitment from the bone marrow: comparison with carrageenan.	2004 Jul	14996947
Thioperamide-elicited increase of histamine release from basolateral amygdala of freely moving rats and its therapeutic implications.	2004 Mar	15054616
Pruritus-associated response mediated by cutaneous histamine H3 receptors.	2004 Mar	15005741
Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in Balb C mice.	2004 May	15066908

Patents

Sample Use Guides

In Vivo Use Guide

mouse: thioperamide (10 μg, i.c.v.). rat: thioperamide (20, 50 μg, i.c.v.). rat: thioperamide (310 µg/kg, i.v.). mouse: thioperamide (10 mg/kg, i.p.)

Route of Administration: Other

In Vitro Use Guide

Thioperamide inhibits firing in rat primary vestibular neurons at nanomolar range and membrane depolarization above 100 µM

Substance Class	Chemical Created by `admin` on `Sat Jun 26 04:58:15 UTC 2021` Edited by `admin` on `Sat Jun 26 04:58:15 UTC 2021`
Record UNII	II4319BWUI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

THIOPERAMIDE

Common Name

English

1-PIPERIDINECARBOTHIOAMIDE, N-CYCLOHEXYL-4-(1H-IMIDAZOL-4-YL)-

Systematic Name

English

MR-12842

Code

English

1-PIPERIDINECARBOTHIOAMIDE, N-CYCLOHEXYL-4-(1H-IMIDAZOL-5-YL)-

Systematic Name

English

Code System Code Type Description

PUBCHEM

3035905