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
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
Caroverine, a multifunctional drug with antioxidant functions.	2003	14757980
[Therapy of olfactory loss].	2003 Aug	12915985
The antioxidant activity of caroverine.	2003 Jan 1	12473379
Pharmacokinetics of caroverine in the inner ear and its effects on cochlear function after systemic and local administrations in Guinea pigs.	2003 Jan-Feb	12566692
Acute treatment of noise trauma with local caroverine application in the guinea pig.	2003 Oct	14606590
Tinnitus: pharmacological topodiagnosis.	2004	15379358
[Drug therapy for disturbances of smelling].	2004 Feb	14999590
[Use of the round window micro cath for inner ear therapy - results of a placebo-controlled, prospective study on chronic tinnitus].	2004 Mar	15042481
Protection of auditory function against noise trauma with local caroverine administration in guinea pigs.	2004 Nov	15504611
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
Topical administration of Caroverine in somatic tinnitus treatment: proof-of-concept study.	2005	16419686
Suppression of tumour-promoting factors in fat-induced colon carcinogenesis by the antioxidants caroverine and ubiquinone.	2005 Jul-Aug	16080529
Low-dose, long-term caroverine administration attenuates impulse noise-induced hearing loss in the rat.	2006 Dec	17050305
Changes in the synaptoarchitectonics of the retina after light-induced damage and their correction with antioxidants of plant origin.	2009 Feb	19140007
Tinnitus: characteristics, causes, mechanisms, and treatments.	2009 Mar	19513328
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
Neuropharmacology of vestibular system disorders.	2010 Mar	20808544

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