ZOLANTIDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H27N3OS
Molecular Weight	381.534
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C(CNC1=NC2=C(S1)C=CC=C2)COC3=CC=CC(CN4CCCCC4)=C3

InChI

InChIKey=KUBONGDXTUOOLM-UHFFFAOYSA-N

InChI=1S/C22H27N3OS/c1-4-13-25(14-5-1)17-18-8-6-9-19(16-18)26-15-7-12-23-22-24-20-10-2-3-11-21(20)27-22/h2-3,6,8-11,16H,1,4-5,7,12-15,17H2,(H,23,24)

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Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2894879 | https://www.ncbi.nlm.nih.gov/pubmed/29162912 | https://www.ncbi.nlm.nih.gov/pubmed/24530460 | https://www.ncbi.nlm.nih.gov/pubmed/15140633

Zolantidine is the novel benzthiazole derivative. It is a centrally acting potent antagonist of histamine at H2-receptors. It was found to be a competitive inhibitor of the histamine catabolising enzyme in brain, histamine N-methyltransferase. High aggression in histamine N-methyltransferase knockout mice was suppressed by treatment with zolantidine, indicating that abnormal histamine H2 receptor activation promoted aggression in knockout mice. Histamine H(3) receptor antagonist JNJ-10181457-induced anxiety-like behaviours were dominantly reduced by zolantidine. Zolantidine significantly attenuated the discriminative stimulus effects of morphine.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histamine H2 receptor 46 Target ID: CHEMBL4654 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2894879	Antagonist 2778	6.3 null [pKi]
Histamine N-methyltransferase 10 Target ID: Q9EST2 Gene ID: 1.00135536E8 Gene Symbol: HNMT Target Organism: Cavia porcellus (Guinea pig) Sources: https://www.ncbi.nlm.nih.gov/pubmed/2894879	Inhibitor 8297	6.6 null [pKi]
Histamine H1 receptor 315 Target ID: P31389 Gene ID: NA Gene Symbol: HRH1 Target Organism: Cavia porcellus (Guinea pig) Sources: https://www.ncbi.nlm.nih.gov/pubmed/2894879	Antagonist 2778	5.1 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24530460	Primary		Preclinical	Unknown Approved Use Unknown
Cholestatic pruritus 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19825905	Palliative		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Histamine H(3)-receptor antagonism improves memory retention and reverses the cognitive deficit induced by scopolamine in a two-trial place recognition task.	2001 Oct 15	11640976
Histamine H(2) -like receptors in chick cerebral cortex: effects on cyclic AMP synthesis and characterization by [(3) H]tiotidine binding.	2002 Jun	12065605
Involvement of histaminergic system in the discriminative stimulus effects of morphine.	2004 May 3	15140633
Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice.	2006 Sep	16806305
Mechanism of the histamine H(3) receptor-mediated increase in exploratory locomotor activity and anxiety-like behaviours in mice.	2014 Jun	24530460
The Histamine H3 Receptor Antagonist E159 Reverses Memory Deficits Induced by Dizocilpine in Passive Avoidance and Novel Object Recognition Paradigm in Rats.	2017	29075190
[Mechanisms of histamine ameliorating memory impairment induced by pentylenetetrazole-kindling epilepsy in rats].	2017 Jan 25	28436624
Histamine N-methyltransferase regulates aggression and the sleep-wake cycle.	2017 Nov 21	29162912

Patents

Sample Use Guides

In Vivo Use Guide

10 mg/kg

Route of Administration: Intraperitoneal

In Vitro Use Guide

Zolantidine also inhibited histamine stimulated adenylate cyclase in a guinea-pig cardiac ventricle homogenate. An IC50 value of 840 ± 60 nM was obtained, corresponding to a Ki value of 52 ± 4 nM, (pKi 7.3).

Name

Type

Language

ZOLANTIDINE

Common Name

English

SKF-95282

Code

English

2-BENZOTHIAZOLAMINE, N-(3-(3-(1-PIPERIDINYLMETHYL)PHENOXY)PROPYL)-

Systematic Name

English

Code System Code Type Description

CAS

104076-38-2