Caroverine HCl
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MedKoo CAT#: 463941

CAS#: 55750-05-5 (HCl)

Description: Caroverine HCl 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. It was discovered in Austria in the 1950s[3] and was developed by Austrian company Phafag AG.


Chemical Structure

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Caroverine HCl
CAS# 55750-05-5 (HCl)

Theoretical Analysis

MedKoo Cat#: 463941
Name: Caroverine HCl
CAS#: 55750-05-5 (HCl)
Chemical Formula: C22H28ClN3O2
Exact Mass: 401.187
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
25.0mg USD 250.0 2 Weeks
50.0mg USD 450.0 2 Weeks
100.0mg USD 750.0 2 Weeks
200.0mg USD 1250.0 2 Weeks
500.0mg USD 2450.0 2 Weeks
1.0g USD 3450.0 2 Weeks
2.0g USD 5650.0 2 Weeks
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Related CAS #: 23465-76-1 (free base)   55750-05-5 (HCl)    

Synonym: P 201-1; P2011; P 2011; 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

Product Data:

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 100.0 248.8

Preparing Stock Solutions

The following data is based on the product molecular weight 401.935 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
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: Kanjanaumporn J, Aeumjaturapat S, Snidvongs K, Seresirikachorn K, Chusakul S. Smell and taste dysfunction in patients with SARS-CoV-2 infection: A review of epidemiology, pathogenesis, prognosis, and treatment options. Asian Pac J Allergy Immunol. 2020 Jun;38(2):69-77. doi: 10.12932/AP-030520-0826. PMID: 32563234.

2: Harless L, Liang J. Pharmacologic treatment for postviral olfactory dysfunction: a systematic review. Int Forum Allergy Rhinol. 2016 Jul;6(7):760-7. doi: 10.1002/alr.21727. Epub 2016 Feb 16. PMID: 26879592.

3: 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.

4: 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.

5: 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.

6: 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.

7: 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.

8: 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.

9: Ehrenberger K, Felix D. Caroverine depresses the activity of cochlear glutamate receptors in guinea pigs: in vivo model for drug-induced neuroprotection? Neuropharmacology. 1992 Dec;31(12):1259-63. doi: 10.1016/0028-3908(92)90054-s. PMID: 1361667.

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

11: Denk DM, Heinzl H, Franz P, Ehrenberger K. Caroverine in tinnitus treatment. A placebo-controlled blind study. Acta Otolaryngol. 1997 Nov;117(6):825-30. doi: 10.3109/00016489709114208. PMID: 9442821.

12: 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.

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: Ikeda N, Kodama I, Shibata S, Kondo N, Yamada K. Electromechanical effects of caroverine, a new slow-channel blockade, on the SA node cells of rabbit and atrial muscle fibers of rabbit and guinea pig. J Cardiovasc Pharmacol. 1982 Jan- Feb;4(1):70-5. doi: 10.1097/00005344-198201000-00012. PMID: 6176803.

15: 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.

16: 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.

17: Koppi S, Eberhardt G, Haller R, König P. Calcium-channel-blocking agent in the treatment of acute alcohol withdrawal--caroverine versus meprobamate in a randomized double-blind study. Neuropsychobiology. 1987;17(1-2):49-52. doi: 10.1159/000118340. PMID: 3306440.

18: 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.

19: Kudo Y, Shibata S. Effects of caroverine and diltiazem on synaptic responses, L-glutamate-induced depolarization and potassium efflux in the frog spinal cord. Br J Pharmacol. 1984 Nov;83(3):813-20. doi: 10.1111/j.1476-5381.1984.tb16237.x. PMID: 6150743; PMCID: PMC1987089.

20: 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.