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Details

Stereochemistry UNKNOWN
Molecular Formula C24H31N5O2
Molecular Weight 421.5362
Optical Activity ( - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OTENZEPAD, (-)-

SMILES

CCN(CC)CC1CCCCN1CC(=O)N2c3ccccc3C(=Nc4cccnc42)O

InChI

InChIKey=UBRKDAVQCKZSPO-UHFFFAOYSA-N
InChI=1S/C24H31N5O2/c1-3-27(4-2)16-18-10-7-8-15-28(18)17-22(30)29-21-13-6-5-11-19(21)24(31)26-20-12-9-14-25-23(20)29/h5-6,9,11-14,18H,3-4,7-8,10,15-17H2,1-2H3,(H,26,31)

HIDE SMILES / InChI

Molecular Formula C24H31N5O2
Molecular Weight 421.5362
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/7786837 | https://www.ncbi.nlm.nih.gov/pubmed/7607735 | https://www.ncbi.nlm.nih.gov/pubmed/2767136

Otenzepad is the first competitive muscarinic M2 antagonist that is cardioselective and had been in phase III clinical trials for the treatment of arrhythmias and bradycardia. Otenzepad was originally developed by Boehringer Ingelheim Pharma KG (Boehringer Ingelheim) in Germany. The parent company is developing oral and IV formulations of the drug for use in symptomatic bradycardia, sinus bradycardia, sick sinus syndrome and symptomatic arrhythmias after intoxication. However, all these research has been discontinued. Otenzepad binds to muscarinic cholinergic receptors in a simple competitive manner. Its affinity for cardiac (M2) muscarinic receptors is about 7 times greater than for ganglionic (M1) receptors and about 36 times greater than for glandular (M3) receptors. The (+)-enantiomer of otenzepad is about 8 times more potent at M2-receptors than the (−)-enantiomer. In a double-blind study, 48 healthy male volunteers were randomised to single oral doses of placebo or otenzepad (120, 240 or 480mg). Heart-rate (HR) was significantly increased by the 250 and 480mg doses (by 15 and 21 beats/minute, respectively). The 480mg dose also increased Diastolic Blood Pressure (DBP) significantly compared with placebo. The oral pharmacokinetics of otenzepad were investigated in a double-blind study in which 48 healthy male volunteers were randomised to single oral doses of placebo or otenzepad (120, 240 or 480mg). Otenzepad bioavailability was 45%, mean residence time (MRT) was 12.5 hours and tmax occurred 2.5 hours postdose.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
208 min
40 mg single, intravenous
dose: 40 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
OTENZEPAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Cardioselective profile of AF-DX 116, a muscarine M2 receptor antagonist.
1986 May 5
Muscarinic binding sites of the pig intravesical ureter.
1995 Oct
Stimulation of cyclic AMP accumulation and phosphoinositide hydrolysis by M3 muscarinic receptors in the rat peripheral lung.
1996 Aug 23
Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line.
1998 Feb
Bone marrow-derived regenerated cardiomyocytes (CMG Cells) express functional adrenergic and muscarinic receptors.
2002 Jan 22
Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegill.
2004 Jul 13
Muscarinic acetylcholine receptor-dependent induction of persistent synaptic enhancement in rat hippocampus in vivo.
2007 Jan 19
Cholinergic properties of soy.
2007 Sep
Structural and functional neuroprotection in glaucoma: role of galantamine-mediated activation of muscarinic acetylcholine receptors.
2010
Patents

Patents

Sample Use Guides

270 to 810 mg/day
Route of Administration: Oral
In Vitro Use Guide
SH-SY5Y neuroblastoma cells were used for activity evaluation. Studies were performed at 37 °C for 20 min in 100mkL assay volumes. Bound and free ligand were separated by vacuum filtration onto Whatman GF/C filters and washed with 2 × 4 ml aliquots of the appropriate buffer. Non-specific binding was defined in the presence of 1 mkmol/1 of atropine sulphate. AFDX-11 (Otenzepad) were used in concentration up to 100mkM.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:37:17 UTC 2021
Edited
by admin
on Fri Jun 25 21:37:17 UTC 2021
Record UNII
WW6A9TFL2C
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OTENZEPAD, (-)-
Common Name English
6H-PYRIDO(2,3-B)(1,4)BENZODIAZEPIN-6-ONE, 11-((2-((DIETHYLAMINO)METHYL)-1-PIPERIDINYL)ACETYL)-5,11-DIHYDRO-, (-)-
Systematic Name English
Code System Code Type Description
FDA UNII
WW6A9TFL2C
Created by admin on Fri Jun 25 21:37:17 UTC 2021 , Edited by admin on Fri Jun 25 21:37:17 UTC 2021
PRIMARY
CAS
122467-13-4
Created by admin on Fri Jun 25 21:37:17 UTC 2021 , Edited by admin on Fri Jun 25 21:37:17 UTC 2021
PRIMARY
Related Record Type Details
RACEMATE -> ENANTIOMER