Details
Stereochemistry | RACEMIC |
Molecular Formula | C17H25NO |
Molecular Weight | 259.3865 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O[C@@H]1CCCC[C@H]1N2CCC(CC2)C3=CC=CC=C3
InChI
InChIKey=YSSBJODGIYRAMI-IAGOWNOFSA-N
InChI=1S/C17H25NO/c19-17-9-5-4-8-16(17)18-12-10-15(11-13-18)14-6-2-1-3-7-14/h1-3,6-7,15-17,19H,4-5,8-13H2/t16-,17-/m1/s1
Molecular Formula | C17H25NO |
Molecular Weight | 259.3865 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Vesamicol is an experimental drug, acting presynaptically by inhibiting acetylcholine (ACh) uptake into synaptic vesicles and reducing its release. Vesamicol (2-[4-phenylpiperidino] cyclohexanol) inhibits the transport of acetylcholine into synaptic vesicles in cholinergic nerve terminals. In addition to its effects on vesicular acetylcholine transport, vesamicol also possesses some sodium channel and alpha-adrenoceptor blocking activity. Vesamicol represents a unique tool for investigating presynaptic mechanisms in cholinergic nerve terminals. Vesamicol induced potent apoptosis of human BACs in cell culture and nude mice models. Vesamicol did not have any effect on EGF or insulin-like growth factor-II-induced growth of human bronchioalveolar carcinomas (BACs). siRNA-mediated attenuation of VAChT reversed the apoptotic activity of vesamicol. Vesamicol inhibited Akt phosphorylation during cell death and that overexpression of constitutively active Akt reversed the apoptotic activity of vesamicol. Disruption of nicotine-induced cholinergic signaling by agents such as vesamicol may have applications in BAC therapy.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26138195 | https://www.ncbi.nlm.nih.gov/pubmed/26872437 | https://www.ncbi.nlm.nih.gov/pubmed/24687885https://www.ncbi.nlm.nih.gov/pubmed/8619013 | https://www.ncbi.nlm.nih.gov/pubmed/9205789 | https://www.ncbi.nlm.nih.gov/pubmed/1925971
Curator's Comment: CNS active in animals
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
2.1 nM [Kd] | |||
Target ID: CHEMBL4767 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7702637 |
2.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
A further study of the neuromuscular effects of vesamicol (AH5183) and of its enantiomer specificity. | 1988 Apr |
|
In vitro characterization of radioiodinated (-)-m-iodovesamicol in rat cerebral membranes. | 1996 |
|
Mutational analysis of aspartate residues in the transmembrane regions and cytoplasmic loops of rat vesicular acetylcholine transporter. | 1999 Jan 8 |
|
Synthesis and evaluation of radiolabeled piperazine derivatives of vesamicol as SPECT agents for cholinergic neurons. | 2001 Apr |
|
In vivo assessment of acetylcholine-releasing function at cardiac vagal nerve terminals. | 2001 Jul |
|
Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters. | 2001 Nov |
|
Opioid receptor regulation of muscarinic acetylcholine receptor-mediated synaptic responses in the hippocampus. | 2001 Oct |
|
Regulation of vesicular acetylcholine transporter by the activation of excitatory amino acid receptors in the avian retina. | 2002 Dec |
|
PET and SPET tracers for mapping the cardiac nervous system. | 2002 Mar |
|
Equilibrium binding and transport studies. | 2003 |
|
Ethanol elevates accumbal dopamine levels via indirect activation of ventral tegmental nicotinic acetylcholine receptors. | 2003 Apr 25 |
|
Choline acetyltransferase: regulation and coupling with protein kinase and vesicular acetylcholine transporter on synaptic vesicles. | 2004 Jan |
|
Choline is transported by vesicular acetylcholine transporter. | 2004 Nov |
|
Release of acetylcholine to raise insulin secretion in Wistar rats by oleanolic acid, one of the active principles contained in Cornus officinalis. | 2006 Aug 14 |
|
Increase of insulin secretion by ginsenoside Rh2 to lower plasma glucose in Wistar rats. | 2006 Jan-Feb |
|
Synthesis and evaluation of vesamicol analog (-)-O-[11C]methylvesamicol as a PET ligand for vesicular acetylcholine transporter. | 2006 Jul |
|
Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine. | 2006 Jun |
|
Evaluation of (+)-p-[11C]methylvesamicol for mapping sigma1 receptors: a comparison with [11C]SA4503. | 2006 May |
|
Mutational and bioinformatics analysis of proline- and glycine-rich motifs in vesicular acetylcholine transporter. | 2006 Sep |
|
First CoMFA characterization of vesamicol analogs as ligands for the vesicular acetylcholine transporter. | 2008 Apr 10 |
|
The epithelial cholinergic system of the airways. | 2008 Aug |
|
A new 18F-labeled fluoroacetylmorpholino derivative of vesamicol for neuroimaging of the vesicular acetylcholine transporter. | 2008 Feb |
|
Neuroimaging of the vesicular acetylcholine transporter by a novel 4-[18F]fluoro-benzoyl derivative of 7-hydroxy-6-(4-phenyl-piperidin-1-yl)-octahydro-benzo[1,4]oxazines. | 2009 Jan |
|
Equilibrium binding and transport by vesicular acetylcholine transporter. | 2010 |
|
Synthesis and in vitro biological evaluation of carbonyl group-containing inhibitors of vesicular acetylcholine transporter. | 2010 Apr 8 |
|
Accessible silanol sites - beneficial for the RP-HPLC separation of constitutional and diastereomeric azaspirovesamicol isomers. | 2010 Dec 10 |
|
Synthesis and biological characterization of a promising F-18 PET tracer for vesicular acetylcholine transporter. | 2015 Aug 1 |
|
Kinetics modeling and occupancy studies of a novel C-11 PET tracer for VAChT in nonhuman primates. | 2016 Feb |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26872437
Curator's Comment: I.p route in rats was used: to assess the effect of vesamicol in vivo, we examined cholinergic parameters, such as the subcellular distribution of ACh, activities of enzymes, uptake of choline, and muscarinic receptor binding in the striatum, hippocampus, and cerebral cortex of rats 30 and 60 min after intraperitoneal injection of vesamicol (3 mg/kg) or of vesamicol in combination with DDVP (5 mg/kg), which was administered 10 min before vasamicol.
https://www.ncbi.nlm.nih.gov/pubmed/9205789
Nonhuman primates: Occupancy studies found that ~0.0057 mg/kg of (-)-vesamicol produced 50% VAChT occupancy in the striatum.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1375854
1. The effects of vesamicol, an inhibitor of vesicular acetylcholine (ACh) storage, were studied on trains of endplate currents (e.p.cs) in the cut rat hemidiaphragm nerve-muscle preparation and on trains of focally recorded nerve terminal current waveforms in the mouse triangularis sterni nerve-muscle preparation. 2. In the rat, 0.1 and 1 microM (-)-vesamicol produced an enhancement of the rundown of e.p.c. amplitudes during trains of high frequency (50 Hz) nerve stimulation. However, 1 microM (+)-vesamicol had no effect on the rundown of e.p.c. amplitudes. 3. In the mouse, high concentrations of (-)-vesamicol (10-100 microM) produced a concentration- and stimulation-dependent decrease in the amplitude of the second negative-going deflection of focally recorded nerve terminal current waveforms. 4. At 1 mM, (-)-vesamicol produced a stimulation-independent decrease in the amplitude of the first negative-going deflection of the nerve terminal current waveforms, an increase in signal delay and evidence of nerve conduction failure. These all indicate a local anaesthetic-like block of nodal Na(+)-channels. 5. In contrast to its effects on trains of e.p.cs, the effects of vesamicol on the nerve terminal current waveforms were not stereoselective, the (+)-isomer being equipotent with the (-)-isomer. 6. Low concentrations of the Na(+)-channel blocking toxin, tetrodotoxin (15-60 nM), produced similar changes in the focally recorded nerve terminal current waveforms to those seen with vesamicol. 7. It is concluded that the stereoselective rundown of e.p.c. amplitudes produced by (-)-vesamicol is due to an effect, either direct or indirect, on ACh mobilization within motor nerve terminals. Furthermore, in mammalian species, the inhibitory effects of vesamicol on nodal Na+-channels which are seen at high concentrations do not contribute to the principal neuromuscular effects of the compound.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 09:55:45 GMT 2023
by
admin
on
Sat Dec 16 09:55:45 GMT 2023
|
Record UNII |
3D416V0FLM
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Code | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
3D416V0FLM
Created by
admin on Sat Dec 16 09:55:46 GMT 2023 , Edited by admin on Sat Dec 16 09:55:46 GMT 2023
|
PRIMARY | |||
|
300000002058
Created by
admin on Sat Dec 16 09:55:46 GMT 2023 , Edited by admin on Sat Dec 16 09:55:46 GMT 2023
|
PRIMARY | |||
|
22232-64-0
Created by
admin on Sat Dec 16 09:55:46 GMT 2023 , Edited by admin on Sat Dec 16 09:55:46 GMT 2023
|
NON-SPECIFIC STEREOCHEMISTRY | |||
|
659840
Created by
admin on Sat Dec 16 09:55:46 GMT 2023 , Edited by admin on Sat Dec 16 09:55:46 GMT 2023
|
PRIMARY | |||
|
Vesamicol
Created by
admin on Sat Dec 16 09:55:46 GMT 2023 , Edited by admin on Sat Dec 16 09:55:46 GMT 2023
|
PRIMARY | |||
|
115362-28-2
Created by
admin on Sat Dec 16 09:55:46 GMT 2023 , Edited by admin on Sat Dec 16 09:55:46 GMT 2023
|
PRIMARY | |||
|
DTXSID701009898
Created by
admin on Sat Dec 16 09:55:46 GMT 2023 , Edited by admin on Sat Dec 16 09:55:46 GMT 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
SALT/SOLVATE -> PARENT | |||
|
ACTIVE ENANTIOMER->RACEMATE |