Caroverine HCl
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MedKoo CAT#: 463941

CAS#: 55750-05-5 (HCl)

Description: Caroverine is a nonselective NMDA and AMPA glutamate receptor antagonist, also acting as a class B calcium-channel-blocker. Pharmacologically, it has been described as a nonspecific calcium channel blocker and as an antagonist of both non-NMDA and NMDA glutamate receptors. Caroverine (Spasmium, Tinnitin, Tinnex) is a muscle-relaxing drug used in Austria and Switzerland to relieve spasms in smooth muscles (which include intestines, arteries, and other organs), and the use in those countries was extended to aid with cerebrovascular diseases there, and eventually to treat tinnitus. caroverine is also a potential chemotherapeutical agent in HNSCC cell lines.

Chemical Structure

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Caroverine HCl
CAS# 55750-05-5 (HCl)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 463941
Name: Caroverine HCl
CAS#: 55750-05-5 (HCl)
Chemical Formula: C22H28ClN3O2
Exact Mass: 401.19
Molecular Weight: 401.935
Elemental Analysis: C, 65.74; H, 7.02; Cl, 8.82; N, 10.45; O, 7.96

Price and Availability

Size Price Availability Quantity
25mg USD 450 2 Weeks
50mg USD 750 2 Weeks
100mg USD 1250 2 Weeks
200mg USD 1950 2 Weeks
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Related CAS #: 23465-76-1 (free base)   55750-05-5 (HCl)    

Synonym: P 201-1; P-201-1; P201-1; P 2011; P-2011; P2011; Caroverine HCl; Spadon; Tinnitin; Tinnex;

IUPAC/Chemical Name: 1-(2-(diethylamino)ethyl)-3-(4-methoxybenzyl)quinoxalin-2(1H)-one hydrochloride

InChi Key: JRNWTJUIMRLKBV-UHFFFAOYSA-N

InChi Code: InChI=1S/C22H27N3O2.ClH/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;1H

SMILES Code: O=C1N(CCN(CC)CC)C2=C(C=CC=C2)N=C1CC3=CC=C(OC)C=C3.[H]Cl

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Product Data
Instruction:
View handling instruction
Biological target: Caroverine hydrochloride is a potent, competitive and reversible antagonist of NMDA and AMPA glutamate receptor.
In vitro activity: The aim of this study was to evaluate the effect of caroverine on HNSCC cell lines. The HNSCC cell lines SCC9, SCC25, CAL27, and FaDu were incubated with caroverine alone or in combination with cisplatin, 5-fluorouracil (5-FU) or cetuximab. Cell viability was measured using the CCK-8 assay. The murine 3T3 fibroblast cell line was used to address tissue specificity. Apoptosis was visualized by immunohistochemistry. Caroverine showed a dose-dependent growth inhibition in all cell lines, IC50 values ranged from 75.69 to 179.80 µM. This effect was increased when caroverine was combined with cetuximab or 5-FU. Immunohistochemistry displayed more apoptosis after caroverine treatment compared to controls. Furthermore, caroverine alone had no growth inhibitory effect on 3T3 cells. For the first time, this study provides evidence that caroverine may serve as a supportive drug in the treatment of HNSCC patients. Reference: Eur Arch Otorhinolaryngol. 2015 Nov;272(11):3451-6. https://dx.doi.org/10.1007/s00405-014-3364-0
In vivo activity: All three groups showed threshold shifts ranging from 50 to 70 dB across frequencies at 1.5, 3 and 6 h after RWM applications, irrespective of whether it was from control or caroverine treatment group. At 24 h after local application, the control group showed a recovery of around 20 dB at all tested frequencies. For the caroverine groups, however, the recovery was much more pronounced. At 24 h the HD group showed a 40–50 dB threshold recovery at 20, 16, 12.5 and 4 kHz, and about 30 dB recovery at 8 kHz. And the threshold recovery was significantly larger than that for the control group at all five frequencies (p < 0.05). In the LD group, the recovery was smaller but was still significant compared to the control group at 24 h at the two highest frequencies (a 20–35 dB recovery at 20 and 16 kHz; p = 0.0004, and p = 0.007, respectively). Reference: Hear Res. 2004 Nov;197(1-2):131-6. https://linkinghub.elsevier.com/retrieve/pii/S0378-5955(04)00208-4

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 248.80

Preparing Stock Solutions

The following data is based on the product molecular weight 401.94 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol: 1. Haymerle G, Thurnher D, Kadletz L, Stanisz I, Brunner M, Kotowski U, Enzenhofer E, Heiduschka G. Assessment of caroverine as a potential chemotherapeutical agent in HNSCC cell lines. Eur Arch Otorhinolaryngol. 2015 Nov;272(11):3451-6. doi: 10.1007/s00405-014-3364-0. Epub 2014 Oct 29. PMID: 25351499.
In vivo protocol: 1. Chen Z, Ulfendahl M, Ruan R, Tan L, Duan M. Protection of auditory function against noise trauma with local caroverine administration in guinea pigs. Hear Res. 2004 Nov;197(1-2):131-6. doi: 10.1016/j.heares.2004.03.021. PMID: 15504611. 2. Duan M, Chen Z, Qiu J, Ulfendahl M, Laurell G, Borg E, Ruan R. Low-dose, long-term caroverine administration attenuates impulse noise-induced hearing loss in the rat. Acta Otolaryngol. 2006 Dec;126(11):1140-7. doi: 10.1080/00016480500540519. PMID: 17050305.

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1: Farrah AY, Al-Mahallawi AM, Basalious EB, Nesseem DI. Investigating the Potential of Phosphatidylcholine-Based Nano-Sized Carriers in Boosting the Oto- Topical Delivery of Caroverine: in vitro Characterization, Stability Assessment and ex vivo Transport Studies. Int J Nanomedicine. 2020 Nov 13;15:8921-8931. doi: 10.2147/IJN.S259172. PMID: 33223827; PMCID: PMC7671472.


2: Nishad RK, Jain AK, Singh M, Verma R, Jain S. Randomised Controlled Clinical Study of Injection Caroverine and Ginkgo Biloba Extract in Cochlear Synaptic Tinnitus. Indian J Otolaryngol Head Neck Surg. 2019 Nov;71(Suppl 2):1523-1528. doi: 10.1007/s12070-019-01655-5. Epub 2019 Apr 13. PMID: 31750210; PMCID: PMC6841866.


3: Raza A, Ansari TM. A novel spectrophotometric determination of caroverine in pharmaceutical formulations via derivatization with Folin-ciocalteu Phenol reagent. Pak J Pharm Sci. 2018 Jan;31(1):153-157. PMID: 29348097.


4: Haymerle G, Thurnher D, Kadletz L, Stanisz I, Brunner M, Kotowski U, Enzenhofer E, Heiduschka G. Assessment of caroverine as a potential chemotherapeutical agent in HNSCC cell lines. Eur Arch Otorhinolaryngol. 2015 Nov;272(11):3451-6. doi: 10.1007/s00405-014-3364-0. Epub 2014 Oct 29. PMID: 25351499.


5: Klement J, Pais I, Hallschmid M, Hubold C, Knispel A, Oltmanns KM, Schultes B, Born J, Peters A. Blocking AMPA receptor signalling by caroverine infusion does not affect counter-regulation of hypoglycaemia in healthy men. Diabetologia. 2009 Jun;52(6):1192-6. doi: 10.1007/s00125-009-1343-6. Epub 2009 Apr 3. PMID: 19343318.


6: Duan M, Chen Z, Qiu J, Ulfendahl M, Laurell G, Borg E, Ruan R. Low-dose, long-term caroverine administration attenuates impulse noise-induced hearing loss in the rat. Acta Otolaryngol. 2006 Dec;126(11):1140-7. doi: 10.1080/00016480500540519. PMID: 17050305.


7: Nohl H, Rohr-Udilova N, Gille L, Bieberschulte W, Jurek D, Marian B, Schulte- Hermann R. Ubiquinol and the papaverine derivative caroverine prevent the expression of tumour- promoting factors in adenoma and carcinoma colon cancer cells induced by dietary fat. Biofactors. 2005;25(1-4):87-95. doi: 10.1002/biof.5520250110. PMID: 16873933.


8: Ehrenberger K. Topical administration of Caroverine in somatic tinnitus treatment: proof-of-concept study. Int Tinnitus J. 2005;11(1):34-7. PMID: 16419686.


9: Nohl H, Rohr-Udilova N, Gille L, Bieberschulte W, Jurek D, Marian B, Schulte- Herman R. Suppression of tumour-promoting factors in fat-induced colon carcinogenesis by the antioxidants caroverine and ubiquinone. Anticancer Res. 2005 Jul-Aug;25(4):2793-800. PMID: 16080529.


10: Chen Z, Ulfendahl M, Ruan R, Tan L, Duan M. Protection of auditory function against noise trauma with local caroverine administration in guinea pigs. Hear Res. 2004 Nov;197(1-2):131-6. doi: 10.1016/j.heares.2004.03.021. PMID: 15504611.


11: Nohl H, Bieberschulte W, Dietrich B, Udilova N, Kozlov AV. Caroverine, a multifunctional drug with antioxidant functions. Biofactors. 2003;19(1-2):79-85. doi: 10.1002/biof.5520190110. PMID: 14757980.


12: Chen Z, Ulfendahl M, Ruan R, Tan L, Duan M. Acute treatment of noise trauma with local caroverine application in the guinea pig. Acta Otolaryngol. 2003 Oct;123(8):905-9. doi: 10.1080/00016480310000638. PMID: 14606590.


13: Kratzer U, Schmidt WJ. Caroverine inhibits the conditioned place aversion induced by naloxone-precipitated morphine withdrawal in rats. Neurosci Lett. 2003 Oct 2;349(2):91-4. doi: 10.1016/s0304-3940(03)00783-3. PMID: 12946560.


14: Chen Z, Duan M, Lee H, Ruan R, Ulfendahl M. Pharmacokinetics of caroverine in the inner ear and its effects on cochlear function after systemic and local administrations in Guinea pigs. Audiol Neurootol. 2003 Jan-Feb;8(1):49-56. doi: 10.1159/000067893. PMID: 12566692.


15: Quint C, Temmel AF, Hummel T, Ehrenberger K. The quinoxaline derivative caroverine in the treatment of sensorineural smell disorders: a proof-of-concept study. Acta Otolaryngol. 2002 Dec;122(8):877-81. PMID: 12542209.


16: Udilova N, Kozlov AV, Bieberschulte W, Frei K, Ehrenberger K, Nohl H. The antioxidant activity of caroverine. Biochem Pharmacol. 2003 Jan 1;65(1):59-65. doi: 10.1016/s0006-2952(02)01452-1. PMID: 12473379.


17: Oestreicher E, Ehrenberger K, Felix D. Different action of memantine and caroverine on glutamatergic transmission in the mammalian cochlea. Adv Otorhinolaryngol. 2002;59:18-25. doi: 10.1159/000059238. PMID: 11885657.


18: Ehrenberger K. Clinical experience with caroverine in inner ear diseases. Adv Otorhinolaryngol. 2002;59:156-62. doi: 10.1159/000059252. PMID: 11885656.


19: König P, Conca A, Lugmayer B. Does a glutamate receptor blocker (Caroverine) enhance haloperidol in the treatment of schizophrenia? Neuropsychobiology. 1999 Sep;40(3):140-1. doi: 10.1159/000026611. PMID: 10494049.


20: Domeisen H, Hotz MA, Häusler R. Caroverine in tinnitus treatment. Acta Otolaryngol. 1998 Jul;118(4):606-8. doi: 10.1080/00016489850154801. PMID: 9726691.