CAROVERINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H27N3O2
Molecular Weight	365.4687
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(CC)CCN1C(=O)C(CC2=CC=C(OC)C=C2)=NC3=C1C=CC=C3

InChI

InChIKey=MSPRUJDUTKRMLM-UHFFFAOYSA-N

InChI=1S/C22H27N3O2/c1-4-24(5-2)14-15-25-21-9-7-6-8-19(21)23-20(22(25)26)16-17-10-12-18(27-3)13-11-17/h6-13H,4-5,14-16H2,1-3H3

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Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25351499
Curator's Comment: description was created based on several sources, including https://www.drugs.com/international/caroverine.html | https://clinicaltrials.gov/ct2/show/NCT01174979 | https://www.ncbi.nlm.nih.gov/pubmed/15042481 | http://www.mims.com/india/drug/info/caroverine?type=full&mtype=generic | https://www.ncbi.nlm.nih.gov/pubmed/9297050

Caroverine is a spasmolytic drug used in tinnitus treatment improves mechanosensitivity and mechanotransduction phenomenon and otoneuroprotective agent. Caroverine acts as an N-type calcium channel blocker, competitive AMPA receptor antagonist, and non-competitive NMDA receptor antagonist. When excessive glutamate binds to NMDA receptors, the receptor opens and allows calcium and sodium to enter the neuron, abnormal levels of calcium disturbs ionic balance causing spontaneous depolarization state. Pathological spontaneous depolarization state is reversed back to physiological polarization state by antagonistic property of Caroverine.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12473379	Antagonist 2778
Glutamate receptor ionotropic AMPA 41 Target ID: CHEMBL2096670 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12473379	Antagonist 2778
Voltage-gated calcium channel 37 Target ID: CHEMBL2363032 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12473379	Blocker 537

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tinnitus 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15042481	Primary		Approved 8429	Spasmium Approved Use Unknown

PubMed

Title	Date	PubMed
Different action of memantine and caroverine on glutamatergic transmission in the mammalian cochlea.	2002	11885657
Clinical experience with caroverine in inner ear diseases.	2002	11885656
The quinoxaline derivative caroverine in the treatment of sensorineural smell disorders: a proof-of-concept study.	2002 Dec	12542209
Sensitive and specific liquid chromatographic-tandem mass spectrometric assay for dihydroergotamine and its major metabolite in human plasma.	2002 Mar 5	11888055
The antioxidant activity of caroverine.	2003 Jan 1	12473379
[Use of the round window micro cath for inner ear therapy - results of a placebo-controlled, prospective study on chronic tinnitus].	2004 Mar	15042481
Re-establishment of olfactory and taste functions.	2005	22073054
Therapy of hearing disorders - conservative procedures.	2005	22073049
Ubiquinol and the papaverine derivative caroverine prevent the expression of tumour- promoting factors in adenoma and carcinoma colon cancer cells induced by dietary fat.	2005	16873933
[Changes of synaptoarchitecture of the retina after the light-induced damage and their correction by plant antioxidants].	2008	19069415
Visual-procedural memory consolidation during sleep blocked by glutamatergic receptor antagonists.	2008 May 21	18495885
Analysis of 60 patients after tympanotomy and sealing of the round window membrane after acute unilateral sensorineural hearing loss.	2009 May-Jun	19410119
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443

Patents

Sample Use Guides

In Vivo Use Guide

Adult: 20-40 mg 3-4 times daily. Max: 200 mg/day. Max Dosage: 200 mg daily.

Route of Administration: Oral

In Vitro Use Guide

Cytotoxicity of caroverine in HNSCC cell lines was assessed using the Cell Counting Kit-8 (CCK-8, Dojindo Molecular Technologies Inc., Rockville, MD, USA). Briefly, 3 9 103 cells were seeded into 96 well plates and allowed to rest for 24 h. Caroverine was dissolved in dimethyl sulfoxide (DMSO) and diluted to concentrations ranging from 50 to 500 mkM. Cells were incubated with increasing doses of caroverine and after 72 h, cell viability was measured using the CCK-8 kit according to the manufacturer’s protocol.

Name

Type

Language

CAROVERINE

Official Name

English

1-(2-(DIETHYLAMINO)ETHYL)-3-(P-METHOXYBENZYL)-2(1H)-QUINOXALINONE

Common Name

English

CAROVERINE [MART.]

Common Name

English

SPASMIUM

Brand Name

English

caroverine [INN]

Common Name

English

Caroverine [WHO-DD]

Common Name

English

CAROVERINE [MI]

Common Name

English

Classification Tree Code System Code

WHO-ATC

A03AX11