TELENZEPINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H22N4O2S
Molecular Weight	370.469
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCN(CC(=O)N2C3=C(C)SC=C3C(=O)NC4=CC=CC=C24)CC1

InChI

InChIKey=VSWPGAIWKHPTKX-UHFFFAOYSA-N

InChI=1S/C19H22N4O2S/c1-13-18-14(12-26-13)19(25)20-15-5-3-4-6-16(15)23(18)17(24)11-22-9-7-21(2)8-10-22/h3-6,12H,7-11H2,1-2H3,(H,20,25)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2695806 | https://www.ncbi.nlm.nih.gov/pubmed/8081076 | https://adisinsight.springer.com/drugs/800000603

Telenzepine is a selective muscarinic M1 receptor antagonist that was studied for selective inhibition of gastric acid secretion. Telenzepine was used in clinical trials in patients with acute duodenal ulcer, where was found that once daily administration of 3 mg in the evening must be regarded as the optimal dosage regimen of telenzepine. However, the preregistration for peptic ulcer in Germany was discontinued. In addition, the drug was studied in patients with nocturnal asthma. It was shown that telenzepine via the oral route at a dose of up to 5 mg was not effective in preventing nocturnal asthma.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Muscarinic acetylcholine receptor M1 169 Target ID: CHEMBL276 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2066986 \| https://www.ncbi.nlm.nih.gov/pubmed/2695806	Antagonist 2778		0.0018 µM [Ki]

PubMed

Title	Date	PubMed
The existence of stable enantiomers of telenzepine and their stereoselective interaction with muscarinic receptor subtypes.	1989 Apr	2704371
Correlation of brain levels of 9-amino-1,2,3,4-tetrahydroacridine (THA) with neurochemical and behavioral changes.	1989 Nov 28	2606156
Assessment of the muscarinic receptor subtypes involved in pilocarpine-induced seizures in mice.	1994 Feb 28	8028781
Characterization of the muscarinic receptor subtype mediating pilocarpine-induced tremulous jaw movements in rats.	1999 Jan 1	9920179
Inhibition of field stimulation-induced contractions of rabbit vas deferens by muscarinic receptor agonists: selectivity of McN-A-343 for M1 receptors.	2001 Apr	11341365
Cholinergic modulation of basal and amphetamine-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens.	2002 Dec 20	12468043
Miniaturization of fluorescence polarization receptor-binding assays using CyDye-labeled ligands.	2003 Aug	14567793
PMA decreases the proliferation of retinal cells in vitro: the involvement of acetylcholine and BDNF.	2003 Jan	12441170
Cholinergic modulation of memory in the basolateral amygdala involves activation of both m1 and m2 receptors.	2003 May	12799522
Muscarinic acetylcholine receptors potentiate the GABAergic transmission in the developing rat inferior colliculus.	2003 Sep	12907311
Muscarinic modulation of nitrergic neurotransmission in guinea-pig gastric fundus.	2004 Apr	15086869
M3 subtype of muscarinic receptors mediate Ca2+ release from intracellular stores in rat prostate neuroendocrine cells.	2005 Apr	15831997
Effect of muscarinic receptor blockade on canine gastric tone and compliance in vivo.	2005 Apr	15683741
N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M1 muscarinic receptors.	2005 Nov	15900318
Effects of muscarinic M1 receptor blockade on cocaine-induced elevations of brain dopamine levels and locomotor behavior in rats.	2007 Apr	17255465
Segment-dependent expression of muscarinic acetylcholine receptors and G-protein coupling in the equine respiratory tract.	2007 Feb	17180451
Muscarinic acetylcholine receptor-dependent induction of persistent synaptic enhancement in rat hippocampus in vivo.	2007 Jan 19	17101232
Muscarinic preferential M(1) receptor antagonists enhance the discriminative-stimulus effects of cocaine in rats.	2007 Oct	17631384
AC260584 (4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one), a selective muscarinic M1 receptor agonist, increases acetylcholine and dopamine release in rat medial prefrontal cortex and hippocampus.	2007 Oct 31	17628522
Modulation of long-term potentiation by individual subtypes of muscarinic acetylcholine receptor in the rat dentate gyrus.	2008	18548582
Muscarinic receptor M1 and phosphodiesterase 1 are key determinants in pulmonary vascular dysfunction following perinatal hypoxia in mice.	2008 Jul	18469116
Acetylcholine mediates the release of IL-8 in human bronchial epithelial cells by a NFkB/ERK-dependent mechanism.	2008 Mar 17	18242599
Effect of muscarinic receptor agonists xanomeline and sabcomeline on acetylcholine and dopamine efflux in the rat brain; comparison with effects of 4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one (AC260584) and N-desmethylclozapine.	2008 Oct 31	18771666
Development of a homogeneous high-throughput live-cell G-protein-coupled receptor binding assay.	2008 Sep	18460694
Galantamine improves apomorphine-induced deficits in prepulse inhibition via muscarinic ACh receptors in mice.	2009 Jan	19133998
Secretion from acinar cells of the exocrine pancreas: role of enteropancreatic reflexes and cholecystokinin.	2009 Jan	18948215
Differential effects of M1 and 5-hydroxytryptamine1A receptors on atypical antipsychotic drug-induced dopamine efflux in the medial prefrontal cortex.	2009 Sep	19491322
Formation and dissociation of M1 muscarinic receptor dimers seen by total internal reflection fluorescence imaging of single molecules.	2010 Feb 9	20133736
[Beneficial effect of galantamine on sensory information-processing deficits].	2010 Oct	20930482

Sample Use Guides

In Vivo Use Guide

120 patients with endoscopically proven, florid duodenal ulcer were treated with either 1.5 mg, 3 mg or 5 mg telenzepine once daily at bedtime (40 patients per dose group).

Route of Administration: Oral

Name

Type

Language

TELENZEPINE

Official Name

English

NSC-758679

Code

English

10H-THIENO(3,4-B)(1,5)BENZODIAZEPIN-10-ONE, 4,9-DIHYDRO-3-METHYL-4-(2-(4-METHYL-1-PIPERAZINYL)ACETYL)-

Common Name

English

TELENZEPINE [MART.]

Common Name

English

telenzepine [INN]

Common Name

English

TELENZEPINE [MI]

Common Name

English

4,9-DIHYDRO-3-METHYL-4-(2-(4-METHYL-1-PIPERAZINYL)ACETYL)-10H-THIENO(3,4-B)(1,5)BENZODIAZEPIN-10-ONE

Systematic Name

English

Telenzepine [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29704