Caroverine is a non-selective NMDA and AMPA glutamate receptor antagonist that also works as a class B calcium channel blocker. Pharmacologically, it is described as a nonspecific calcium channel blocker and an antagonist of non-NMDA and NMDA glutamate receptors. Carvacine (Spasmium, Tinnitin, Tinnex) is a muscle relaxant drug used in Austria and Switzerland to relieve spasms of smooth muscles (including intestines, arteries, and other organs), where its use has expanded to help treat cerebral blood vessels The disease is there, and eventually tinnitus is treated. Carvacine is also a potential chemotherapeutic agent for HNSCC cell lines.

Physicochemical Properties

Molecular Formula	C22H28CLN3O2
Molecular Weight	401.935
Exact Mass	401.187
Elemental Analysis	C, 65.74; H, 7.02; Cl, 8.82; N, 10.45; O, 7.96
CAS #	55750-05-5
Related CAS #	23465-76-1;55750-05-5 (HCl);
PubChem CID	3043582
Appearance	White to off-white solid powder
Density	1.11g/cm3
Boiling Point	521.2ºC at 760mmHg
Flash Point	269ºC
LogP	4.139
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	8
Heavy Atom Count	28
Complexity	510
Defined Atom Stereocenter Count	0
SMILES	CCN(CC)CCN1C2=CC=CC=C2N=C(C1=O)CC3=CC=C(C=C3)OC.Cl
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
Chemical Name	1-(2-(diethylamino)ethyl)-3-(4-methoxybenzyl)quinoxalin-2(1H)-one hydrochloride
Synonyms	P 201-1; P-201-1; P201-1; P 2011; P-2011; P2011; Caroverine HCl; Spadon; Tinnitin; Tinnex;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In rat hindquarter preparations, carvacrol (1 μM; 10 min pretreatment) decreases the pressor response to KCl (80 mM) and norepinephrine (1 μM). In isolated rat aortas, carvacine dramatically reduces the contraction caused by KCl (40 mM) [3].
ln Vivo	Caroverine (1.44 mg/rat; subcutaneous injection; 1.0 mL/h for 72 hours) can reduce impulse noise-induced hearing loss in rats [4].
Animal Protocol	Animal/Disease Models: SD (SD (Sprague-Dawley)) rats (250-300 g) of either sex underwent pulsed noise exposure [4] Doses: 1.44 mg/rat Doses: 20 mg/mL; sc 1.0 mL/h for 72 hrs (hrs (hours)) Experimental Results: Significant protection of the cochlea from impulse noise damage.
References	[1]. Pharmacokinetics of caroverine in the inner ear and its effects on cochlear function after systemic and local administrations in Guinea pigs. Audiol Neurootol. Jan-Feb 2003;8(1):49-56. [2]. Caroverine in tinnitus treatment. A placebo-controlled blind study. Acta Otolaryngol. 1997 Nov;117(6):825-30. [3]. Vasorelaxant action of caroverine fumarate (a quinoxaline derivative), a calcium-blocking agent. Br J Pharmacol. 1980;71(1):343-8. [4]. Low-dose, long-term caroverine administration attenuates impulse noise-induced hearing loss in the rat. Acta Otolaryngol. 2006 Dec;126(11):1140-7.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~248.80 mM) H2O : ~20 mg/mL (~49.76 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4879 mL	12.4397 mL	24.8793 mL
	5 mM	0.4976 mL	2.4879 mL	4.9759 mL
	10 mM	0.2488 mL	1.2440 mL	2.4879 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.