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

HIDE SMILES / InChI

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 2849
Glutamate receptor ionotropic AMPA 42 Target ID: CHEMBL2096670 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12473379	Antagonist 2849
Voltage-gated calcium channel 37 Target ID: CHEMBL2363032 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12473379	Blocker 555

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tinnitus 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15042481	Primary		Approved 8583	Spasmium Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
18.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12566692/	12.8 OTHER single, topical dose: 12.8 OTHER route of administration: Topical experiment type: SINGLE co-administered:		CAROVERINE	Cavia porcellus population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
120 mg single, oral Highest studied dose Dose: 120 mg Route: oral Route: single Dose: 120 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8838434/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8838434/	Sources: https://pubmed.ncbi.nlm.nih.gov/8838434/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 429	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/65709#section=Biological-Test-Results Page: 44.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/65709#section=Biological-Test-Results Page: 61.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/65709#section=Biological-Test-Results Page: 61.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/65709#section=Biological-Test-Results Page: 4.0	yes [IC50 7.5637 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/65709#section=Biological-Test-Results Page: 46 \| 54	no

PubMed

Title	Date	PubMed
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010-12	21818443
Neuropharmacology of vestibular system disorders.	2010-03	20808544
Blocking AMPA receptor signalling by caroverine infusion does not affect counter-regulation of hypoglycaemia in healthy men.	2009-06	19343318
Tinnitus: characteristics, causes, mechanisms, and treatments.	2009-03	19513328
Changes in the synaptoarchitectonics of the retina after light-induced damage and their correction with antioxidants of plant origin.	2009-02	19140007
Visual-procedural memory consolidation during sleep blocked by glutamatergic receptor antagonists.	2008-05-21	18495885
[Changes of synaptoarchitecture of the retina after the light-induced damage and their correction by plant antioxidants].	2008	19069415
Analysis of 60 patients after tympanotomy and sealing of the round window membrane after acute unilateral sensorineural hearing loss.	2007-12-23	19410119
Low-dose, long-term caroverine administration attenuates impulse noise-induced hearing loss in the rat.	2006-12	17050305
Suppression of tumour-promoting factors in fat-induced colon carcinogenesis by the antioxidants caroverine and ubiquinone.	2005-08-06	16080529
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
Protection of auditory function against noise trauma with local caroverine administration in guinea pigs.	2004-11	15504611
[Use of the round window micro cath for inner ear therapy - results of a placebo-controlled, prospective study on chronic tinnitus].	2004-03	15042481
[Drug therapy for disturbances of smelling].	2004-02	14999590
Tinnitus: pharmacological topodiagnosis.	2004	15379358
Caroverine inhibits the conditioned place aversion induced by naloxone-precipitated morphine withdrawal in rats.	2003-10-02	12946560
Acute treatment of noise trauma with local caroverine application in the guinea pig.	2003-10	14606590
[Therapy of olfactory loss].	2003-08	12915985
The antioxidant activity of caroverine.	2003-01-01	12473379
Caroverine, a multifunctional drug with antioxidant functions.	2003	14757980
The quinoxaline derivative caroverine in the treatment of sensorineural smell disorders: a proof-of-concept study.	2002-12	12542209
Pharmacokinetics of caroverine in the inner ear and its effects on cochlear function after systemic and local administrations in Guinea pigs.	2002-03-06	12566692
Sensitive and specific liquid chromatographic-tandem mass spectrometric assay for dihydroergotamine and its major metabolite in human plasma.	2002-03-05	11888055
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

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

SPASMIUM

Preferred Name

English

CAROVERINE

Official Name

English

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

Common Name

English

CAROVERINE [MART.]

Common 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