Caroverine: Difference between revisions
removed Category:Phenol ethers; added Category:4-Methoxyphenyl compounds using HotCat |
|||
(44 intermediate revisions by 18 users not shown) | |||
Line 1: | Line 1: | ||
{{Short description|Chemical compound}} |
|||
{{Drugbox |
{{Drugbox |
||
| Verifiedfields = changed |
| Verifiedfields = changed |
||
Line 36: | Line 37: | ||
<!--Chemical data--> |
<!--Chemical data--> |
||
| C=22 | H=27 | N=3 | O=2 |
| C=22 | H=27 | N=3 | O=2 |
||
| molecular_weight = 365.47 g/mol |
|||
| smiles = O=C/1N(c3c(\N=C\1Cc2ccc(OC)cc2)cccc3)CCN(CC)CC |
| smiles = O=C/1N(c3c(\N=C\1Cc2ccc(OC)cc2)cccc3)CCN(CC)CC |
||
}} |
}} |
||
'''Caroverine''' ('''Spasmium''', '''Tinnitin''', '''Tinnex''') is a [[Antispasmodic|muscle-relaxing drug]] used in Austria and Switzerland to relieve [[spasm]]s in [[smooth muscle]]s (which include intestines, arteries, and other organs), and the use in those countries was extended to aid with [[cerebrovascular disease]]s there, and eventually to treat [[tinnitus]].<ref name=Martindale36/> It is also used to treat tinnitus in India. |
|||
'''Caroverine''' ('''Spasmium''', '''Spadon''', '''Tinnex''') is a [[drug]] used in Tinnitus treatment improves mechanosensitivity and mechanotransduction phenomenon and ''otoneuroprotective'' ([[inner ear]] [[neuroprotection|protective]]) agent in some countries.<ref name=pmid12473379>{{ cite journal | author = Udilova N, Kozlov AV, Bieberschulte W, Frei K, Ehrenberger K, Nohl H | title = The Antioxidant Activity of Caroverine | journal = [[Biochemical Pharmacology]] | year = 2003 | volume = 65 | issue = 1 | pages = 59–65 | pmid = 12473379 | doi = 10.1016/S0006-2952(02)01452-1 }}</ref> It acts as an [[N-type calcium channel]] [[calcium channel blocker|blocker]], [[competitive inhibition|competitive]] [[AMPA receptor#Antagonists|AMPA receptor antagonist]], and [[non-competitive inhibition|non-competitive]] [[NMDA receptor antagonist]].<ref name=pmid12473379/> It also has potent [[antioxidant]] effects.<ref name=pmid12473379/><ref name=pmid14757980>{{ cite journal | author = Nohl H, Bieberschulte W, Dietrich B, Udilova N, Kozlov AV | title = Caroverine, a Multifunctional Drug with Antioxidant Functions | journal = BioFactors | year = 2003 | volume = 19 | issue = 1–2 | pages = 79–85 | pmid = 14757980 | doi = 10.1002/biof.5520190110 }}</ref> |
|||
Chemically, it is a quinoxalineone<ref>{{cite book | vauthors = Bungardt E, Mutschler E |chapter=Spasmolytics |title=Ullmann's Encyclopedia of Industrial Chemistry |date=15 June 2000 |doi=10.1002/14356007.a24_515 |publisher=Wiley|page=11|isbn=978-3527306732 }}</ref> and is available in both a base and [[hydrochloric acid]] forms.<ref name=Martindale36>{{cite book | veditors = Sweetman SC |title=Martindale |date=2009 |publisher=Pharmaceutical Press |isbn=9780853698401 |page=2277 |edition= 36th}}</ref> |
|||
Caroverine [1-(diethylaminoethyl) -3 – (p-methoxybenzyl) – 1, 2 – hydroquinoxaline-2-one] is a quinoxaline derivative developed in the 1960s. Caroverine, an N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist together with antioxidant activity, has been shown to protect the inner ear from excitotoxicity and to be effective in the treatment of tinnitus, sudden hearing loss and speech discrimination disorders in presbyacusis. |
|||
Pharmacologically, it has been described as a nonspecific [[calcium channel blocker]] and as an antagonist of both non-[[NMDA]] and NMDA [[glutamate receptor]]s.<ref name=Dobie1999/><ref name=Langguth2009/> |
|||
In recent years, it is on grounds of its quinoxline-dione structure, glutamate antagonism of him excitatory, afferent synapses of the cochlear inner hair cells and its neuroprotective properties that caroverine has been investigated as a new drug in the pharmacological treatment of tinnitus. |
|||
It was discovered in Austria in the 1950s<ref name=Dobie1999/> and was [[drug development|developed]] by Austrian company Phafag AG.<ref name=Dobie1999/> |
|||
Caroverine also acts as a reversible glutamate antagonist in afferent cochlear synapse. Theoretical justification for the introduction of caroverine in the pharmacotherapy of tinnitus is that glutamate, as a key neurotransmitter in the central nervous system, is the most likely transmitter-substance in the afferent cochlear synapse (Ehrenberger-K eta al., 1992; Ehrenberger-K et al., 1995a; Ehrenberger-K et al., 1995b). |
|||
Its INN name, caroverine, was proposed in 1972.<ref>{{cite journal |title=Proposed INNs List 28 |journal=WHO Chronicle |date=1972 |volume=26 |issue=9 |url=https://www.who.int/medicines/publications/druginformation/innlists/PL28.pdf}}</ref> |
|||
==Application== |
|||
Caroverine has been demonstrated to have a high rate of efficacy in the treatment of cochlear-synaptic tinnitus.<ref>{{cite journal |title=Caroverine in tinnitus treatment. A placebo-controlled blind study. |author=Denk DM, Heinzl H, Franz P, Ehrenberger K. |date=Nov 1997 |journal=Acta Oto-Laryngologica |PMID=9442821 |volume=117 |pages=825–30 |doi=10.3109/00016489709114208}}</ref> |
|||
An intravenous formulation was tested in a single-blinded study in tinnitus that published in 1997 and had positive results; an effort to replicate those results failed to show any effect,<ref name=Langguth2009>{{cite journal | vauthors = Langguth B, Salvi R, Elgoyhen AB | title = Emerging pharmacotherapy of tinnitus | journal = Expert Opinion on Emerging Drugs | volume = 14 | issue = 4 | pages = 687–702 | date = December 2009 | pmid = 19712015 | pmc = 2832848 | doi = 10.1517/14728210903206975 }}</ref> and more people had their condition worsen than experienced benefit.<ref name=Dobie1999>{{cite journal | vauthors = Dobie RA | title = A review of randomized clinical trials in tinnitus | journal = The Laryngoscope | volume = 109 | issue = 8 | pages = 1202–1211 | date = August 1999 | pmid = 10443820 | doi = 10.1097/00005537-199908000-00004 | s2cid = 21409406 }}</ref> Pilot studies using a spray formulation for tinnitus published in 2005.<ref>{{cite book | vauthors = Darlington CL, Smith PF | title = Tinnitus: Pathophysiology and Treatment | chapter = Drug treatments for tinnitus | series = Progress in Brain Research | volume = 166 | pages = 249–262 | date = 2007 | pmid = 17956789 | doi = 10.1016/S0079-6123(07)66023-3 | isbn = 9780444531674 }}</ref> |
|||
Caroverine is available in Injection and Capsule form. |
|||
In 2010 Phafag licensed rights to caroverine to the Indian company, Lincoln Pharmaceuticals, to develop the drug for tinnitus in India.<ref>{{cite news |title=Press release: Lincoln Pharma ties up with Swiss Phafag for Tinnitin injections |url=https://www.business-standard.com/article/companies/lincoln-pharma-ties-up-with-swiss-phafag-for-tinnitin-injections-110111700044_1.html |work=Lincoln via Business Standard India |date=17 November 2010}}</ref> Lincoln first marketed it for that purpose in India in 2011.<ref>{{cite news |title=Press Release: Lincoln Pharma launches Tinnex Injection |url=https://www.business-standard.com/article/press-releases/lincoln-pharma-launches-tinnex-injection-111041400145_1.html |work=Lincoln via Business Standard India |date=14 April 2011}}</ref> |
|||
==See also== |
|||
* [[Quinoxalinedione]] |
|||
As of 2016 it had been studied in a small clinical trial in people with [[anosmia|loss of the sense of smell]].<ref>{{cite journal | vauthors = Harless L, Liang J | title = Pharmacologic treatment for postviral olfactory dysfunction: a systematic review | journal = International Forum of Allergy & Rhinology | volume = 6 | issue = 7 | pages = 760–767 | date = July 2016 | pmid = 26879592 | doi = 10.1002/alr.21727 | s2cid = 29620152 }}</ref> |
|||
⚫ | |||
⚫ | |||
As of 2018 it was marketed under the brand names Spasmium and Tinnitin in Austria, and under the brand Tinnex in India.<ref>{{cite web |title=Caroverine International Brands |url=https://www.drugs.com/international/caroverine.html |publisher=Drugs.com |access-date=14 July 2018}}</ref> |
|||
⚫ | |||
⚫ | |||
{{Muscle relaxants}} |
{{Muscle relaxants}} |
||
{{ |
{{Ion channel modulators}} |
||
{{Ionotropic glutamate receptor modulators}} |
|||
{{Glutamatergics}} |
|||
[[Category:Quinoxalines]] |
[[Category:Quinoxalines]] |
||
[[Category:Lactams]] |
[[Category:Lactams]] |
||
[[Category: |
[[Category:4-Methoxyphenyl compounds]] |
||
[[Category:AMPA receptor antagonists]] |
[[Category:AMPA receptor antagonists]] |
||
[[Category:NMDA receptor antagonists]] |
[[Category:NMDA receptor antagonists]] |
||
[[Category:Diethylamino compounds]] |
Latest revision as of 20:07, 23 September 2024
Clinical data | |
---|---|
Routes of administration | Oral |
ATC code | |
Legal status | |
Legal status |
|
Identifiers | |
| |
CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.164.389 |
Chemical and physical data | |
Formula | C22H27N3O2 |
Molar mass | 365.477 g·mol−1 |
3D model (JSmol) | |
| |
| |
(what is this?) (verify) |
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.[1] It is also used to treat tinnitus in India.
Chemically, it is a quinoxalineone[2] and is available in both a base and hydrochloric acid forms.[1]
Pharmacologically, it has been described as a nonspecific calcium channel blocker and as an antagonist of both non-NMDA and NMDA glutamate receptors.[3][4]
It was discovered in Austria in the 1950s[3] and was developed by Austrian company Phafag AG.[3]
Its INN name, caroverine, was proposed in 1972.[5]
An intravenous formulation was tested in a single-blinded study in tinnitus that published in 1997 and had positive results; an effort to replicate those results failed to show any effect,[4] and more people had their condition worsen than experienced benefit.[3] Pilot studies using a spray formulation for tinnitus published in 2005.[6]
In 2010 Phafag licensed rights to caroverine to the Indian company, Lincoln Pharmaceuticals, to develop the drug for tinnitus in India.[7] Lincoln first marketed it for that purpose in India in 2011.[8]
As of 2016 it had been studied in a small clinical trial in people with loss of the sense of smell.[9]
As of 2018 it was marketed under the brand names Spasmium and Tinnitin in Austria, and under the brand Tinnex in India.[10]
References
[edit]- ^ a b Sweetman SC, ed. (2009). Martindale (36th ed.). Pharmaceutical Press. p. 2277. ISBN 9780853698401.
- ^ Bungardt E, Mutschler E (15 June 2000). "Spasmolytics". Ullmann's Encyclopedia of Industrial Chemistry. Wiley. p. 11. doi:10.1002/14356007.a24_515. ISBN 978-3527306732.
- ^ a b c d Dobie RA (August 1999). "A review of randomized clinical trials in tinnitus". The Laryngoscope. 109 (8): 1202–1211. doi:10.1097/00005537-199908000-00004. PMID 10443820. S2CID 21409406.
- ^ a b Langguth B, Salvi R, Elgoyhen AB (December 2009). "Emerging pharmacotherapy of tinnitus". Expert Opinion on Emerging Drugs. 14 (4): 687–702. doi:10.1517/14728210903206975. PMC 2832848. PMID 19712015.
- ^ "Proposed INNs List 28" (PDF). WHO Chronicle. 26 (9). 1972.
- ^ Darlington CL, Smith PF (2007). "Drug treatments for tinnitus". Tinnitus: Pathophysiology and Treatment. Progress in Brain Research. Vol. 166. pp. 249–262. doi:10.1016/S0079-6123(07)66023-3. ISBN 9780444531674. PMID 17956789.
- ^ "Press release: Lincoln Pharma ties up with Swiss Phafag for Tinnitin injections". Lincoln via Business Standard India. 17 November 2010.
- ^ "Press Release: Lincoln Pharma launches Tinnex Injection". Lincoln via Business Standard India. 14 April 2011.
- ^ Harless L, Liang J (July 2016). "Pharmacologic treatment for postviral olfactory dysfunction: a systematic review". International Forum of Allergy & Rhinology. 6 (7): 760–767. doi:10.1002/alr.21727. PMID 26879592. S2CID 29620152.
- ^ "Caroverine International Brands". Drugs.com. Retrieved 14 July 2018.