Details
Stereochemistry | RACEMIC |
Molecular Formula | C24H31N5O2 |
Molecular Weight | 421.5352 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN(CC)CC1CCCCN1CC(=O)N2C3=CC=CC=C3C(=O)NC4=CC=CN=C24
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)
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/10566053Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10566053
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23379472 |
537.0 nM [Ki] | ||
Target ID: CHEMBL211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23379472 |
81.0 nM [Ki] | ||
Target ID: CHEMBL245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23379472 |
2089.0 nM [Ki] | ||
Target ID: CHEMBL1821 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23379472 |
407.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
T1/2
Value | Dose | Co-administered | Analyte | Population |
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208 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1914372 |
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 |
PubMed
Title | Date | PubMed |
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Cardioselective profile of AF-DX 116, a muscarine M2 receptor antagonist. | 1986 May 5 |
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Cloned M1 muscarinic receptors mediate both adenylate cyclase inhibition and phosphoinositide turnover. | 1988 Oct |
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Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells. | 1989 Apr |
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Correlation of brain levels of 9-amino-1,2,3,4-tetrahydroacridine (THA) with neurochemical and behavioral changes. | 1989 Nov 28 |
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Cloning of the rat M3, M4 and M5 muscarinic acetylcholine receptor genes by the polymerase chain reaction (PCR) and the pharmacological characterization of the expressed genes. | 1992 |
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Muscarinic binding sites of the pig intravesical ureter. | 1995 Oct |
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Stimulation of cyclic AMP accumulation and phosphoinositide hydrolysis by M3 muscarinic receptors in the rat peripheral lung. | 1996 Aug 23 |
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Effects of a cardioselective M2 receptor antagonist, AF-DX 116, on ventricular arrhythmias in dogs. | 1997 |
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Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line. | 1998 Feb |
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Bone marrow-derived regenerated cardiomyocytes (CMG Cells) express functional adrenergic and muscarinic receptors. | 2002 Jan 22 |
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Regeneration of cardiomyocytes from bone marrow: Use of mesenchymal stem cell for cardiovascular tissue engineering. | 2003 Mar |
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Potentiation of the osmosensitive release of taurine and D-aspartate from SH-SY5Y neuroblastoma cells after activation of M3 muscarinic cholinergic receptors. | 2004 Dec |
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Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegill. | 2004 Jul 13 |
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Activation of muscarinic cholinergic receptors inhibits giant neurones in the caudal pontine reticular nucleus. | 2006 Oct |
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Muscarinic acetylcholine receptor-dependent induction of persistent synaptic enhancement in rat hippocampus in vivo. | 2007 Jan 19 |
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Cholinergic properties of soy. | 2007 Sep |
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Functional characterization of muscarinic autoreceptors in rat and human neocortex. | 2009 Aug |
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Structural and functional neuroprotection in glaucoma: role of galantamine-mediated activation of muscarinic acetylcholine receptors. | 2010 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10566053
270 to 810 mg/day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2767136
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.
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NCI_THESAURUS |
C29704
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C75279
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107867
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DTXSID0045674
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102394-31-0
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100158-38-1
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Otenzepad
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CHEMBL17045
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SUB09478MIG
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OM7J0XAL0S
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6488
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100000083555
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ACTIVE MOIETY