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{{drugbox
{{Drugbox
| IUPAC_name       = 2-(2-chlorophenyl)-2-(methylamino)cyclohexanone
| Verifiedfields = changed
| image             = S-ketamine-2D-skeletal.png
| Watchedfields = changed
| image2            = S-ketamine-3D-balls.png
| verifiedrevid = 461095357
| width            = 180
| IUPAC_name = (''S'')-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone
| CAS_number       = 33643-46-8
| image = Esketamine2DCSD.svg
| ATC_prefix       = N01
| width = 180
| ATC_suffix       = AX14  
| image2 = S-ketamine-3D-balls.png
| PubChem           = 182137
| drug_name = Esketamine
| DrugBank         =  
 
| C=13|H=16|Cl=1|N=1|O=1
<!--Clinical data-->
| molecular_weight = 237.725 g/mol
| tradename = Ketanest S
| bioavailability  =  
| Drugs.com = {{drugs.com|CDI|ketamine}}
| protein_bound    =  
 
| metabolism        =  
<!--Identifiers-->
| elimination_half-life =  
| CAS_number_Ref = {{cascite|changed|??}}
| excretion        =  
| CAS_number = 33643-46-8
| pregnancy_AU      = <!-- A / B1 / B2 / B3 / C / D / X -->
| ATC_prefix = N01
| pregnancy_US      =  <!-- A / B            / C / D / X -->
| ATC_suffix = AX14
| pregnancy_category= 
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| legal_AU          =  <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| ChEMBL = 742
| legal_CA          =  <!--             / Schedule I, II, III, IV, V, VI, VII, VIII -->
| PubChem = 182137
| legal_UK          = <!-- GSL        / P      / POM / CD / Class A, B, C -->
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| legal_US          =  <!-- OTC                  / Rx-only  / Schedule I, II, III, IV, V -->
| DrugBank = DB01221
| legal_status      =  
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| routes_of_administration =  
| ChemSpiderID = 158414
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 50LFG02TXD
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 6121
 
<!--Chemical data-->
| C=13 | H=16 | Cl=1 | N=1 | O=1  
| molecular_weight = 237.725 g/mol
| smiles = CN[C@](C1=C(Cl)C=CC=C1)(CCCC2)C2=O
| InChI = 1/C13H16ClNO/c1-15-13(9-5-4-8-12(13)16)10-6-2-3-7-11(10)14/h2-3,6-7,15H,4-5,8-9H2,1H3
| InChIKey = YQEZLKZALYSWHR-UHFFFAOYAB
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C13H16ClNO/c1-15-13(9-5-4-8-12(13)16)10-6-2-3-7-11(10)14/h2-3,6-7,15H,4-5,8-9H2,1H3/t13-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = YQEZLKZALYSWHR-ZDUSSCGKSA-N
}}
}}
'''Esketamine''' (trade name '''Ketanest S''') is a [[general anaesthetic]]. It is the ''S''-[[enantiomer]] of [[ketamine]].


{{pharmacology-stub}}
{{Main|Ketamine}}
'''Esketamine'''  (also '''(''S'')-ketamine''' or '''''S''(+)-ketamine''') (brand name '''Ketanest S''') is a [[general anaesthetic]] and a [[dissociative]]. It is the S(+) [[enantiomer]] of the drug [[ketamine]], a general anaesthetic. Esketamine acts primarily as a [[Receptor antagonist#Non-competitive|non-competitive]] [[NMDA receptor antagonist]], but is also a [[dopamine reuptake inhibitor]]. As of July 2014, it is in [[Phases of clinical research#Phase_II|phase II]] [[clinical trial]]s for [[treatment-resistant depression]] (TRD).<ref name="issn2168-9709">{{cite journal | author = Wijesinghe, R | year = 2014 | title = Emerging Therapies for Treatment Resistant Depression | url = http://cpnp.org/resource/mhc/2014/09/emerging-therapies-treatment-resistant-depression | journal = Ment Health Clin | publisher = | volume = 4 | issue = 5 | page = 56 | issn = 2168-9709}}</ref>
 
==Pharmacology==
Esketamine is approximately twice as potent as [[racemic mixture|racemic]] ketamine.<ref name="clinical_use">{{cite pmid|9893910}}</ref> It is eliminated from the human body more quickly than R(−)-ketamine or racemic ketamine, although R(−)-ketamine slows its elimination.<ref>{{cite pmid|11719729}}</ref>
 
A number of studies have suggested that esketamine has a more medically useful pharmacological action than R(−)-ketamine or racemic ketamine. Esketamine inhibits [[dopamine transporter]]s eight times more than R(−)-ketamine.<ref>{{cite pmid|10553955}}</ref> This increases dopamine activity in the brain. At doses causing the same intensity of effects, esketamine is generally considered to be more pleasant by patients.<ref name="vigilance">{{cite pmid|1443509}}</ref><ref>{{cite pmid|7840417}}</ref> Patients also generally recover mental function more quickly after being treated with pure esketamine, which may be a result of the fact that it is cleared from their system more quickly.<ref name="clinical_use" /><ref name="pharma" />
 
Esketamine has an affinity for the PCP binding site of the [[NMDA receptor]] 3-4 times higher than that of R(−)-ketamine. Unlike R(−)-ketamine, esketamine does not bind significantly to [[sigma receptor]]s. Esketamine increases [[glucose]] metabolism in [[frontal cortex]], while R(−)-ketamine decreases glucose metabolism in the brain. This difference may be responsible for the fact that esketamine generally has a more dissociative or [[hallucinogenic]] effect while R(−)-ketamine is reportedly more relaxing.<ref name="pharma">{{cite pmid|9088882}}</ref> However, other studies have found no difference between the isomers in the patient's level of vigilance.<ref name="vigilance" />
 
==Potential use as an antidepressant==
{{main|Ketamine#Antidepressant use}}
[[Johnson & Johnson]] is developing a nasal spray formulation of esketamine as a treatment for [[depression (mood)|depression]] in patients that have been unresponsive to other antidepressants in the [[United States]].<ref name="issn2168-9709" /> As of July 2014, phase II clinical trials of intranasal esketamine sponsored by the Johnson & Johnson subsidiary [[Janssen Pharmaceutica]] are underway.<ref name="issn2168-9709" /><ref>http://clinicaltrials.gov/show/NCT01998958</ref> Other pharmaceutical companies are also developing new antidepressant drugs that act similarly to ketamine, including [[Naurex]]'s [[rapastinel]] (GLYX-13) and [[NRX-1074]], and [[Cerecor]]'s [[CERC-301]].<ref name="issn2168-9709" />
 
Although most studies suggest that esketamine is preferable for medical uses, a 2013 study found that the antidepressant effect of R(−)-ketamine lasted longer than those of S(+)-ketamine in mice.<ref>{{cite pmid|24316345}}</ref>
 
==See also==
* [[ALKS-5461]]
* [[CERC-501]]
* [[NSI-189]]
 
==References==
{{Reflist|2}}
 
 
{{General anesthetics}}
{{General anesthetics}}
{{Hallucinogens}}
{{Antidepressants}}
{{Dopaminergics}}
{{Glutamatergics}}


[[Category:Anesthetics]]
[[Category:General anesthetics]]
[[Category:Dissociatives]]
[[Category:Dissociative drugs]]
[[Category:Dopamine reuptake inhibitors]]
[[Category:NMDA receptor antagonists]]
[[Category:NMDA receptor antagonists]]
[[Category:Sedatives]]
[[Category:Sedatives]]
[[Category:Ketones]]
[[Category:Organochlorides]]
[[Category:Amines]]
[[Category:Enantiopure drugs]]
[[Category:Antidepressants]]

Revision as of 15:38, 8 April 2015

Esketamine
File:Esketamine2DCSD.svg
File:S-ketamine-3D-balls.png
Clinical data
Trade namesKetanest S
AHFS/Drugs.comConsumer Drug Information
ATC code
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC13H16ClNO
Molar mass237.725 g/mol
3D model (JSmol)
 ☒N☑Y (what is this?)  (verify)
Main article: Ketamine

Esketamine (also (S)-ketamine or S(+)-ketamine) (brand name Ketanest S) is a general anaesthetic and a dissociative. It is the S(+) enantiomer of the drug ketamine, a general anaesthetic. Esketamine acts primarily as a non-competitive NMDA receptor antagonist, but is also a dopamine reuptake inhibitor. As of July 2014, it is in phase II clinical trials for treatment-resistant depression (TRD).[1]

Pharmacology

Esketamine is approximately twice as potent as racemic ketamine.[2] It is eliminated from the human body more quickly than R(−)-ketamine or racemic ketamine, although R(−)-ketamine slows its elimination.[3]

A number of studies have suggested that esketamine has a more medically useful pharmacological action than R(−)-ketamine or racemic ketamine. Esketamine inhibits dopamine transporters eight times more than R(−)-ketamine.[4] This increases dopamine activity in the brain. At doses causing the same intensity of effects, esketamine is generally considered to be more pleasant by patients.[5][6] Patients also generally recover mental function more quickly after being treated with pure esketamine, which may be a result of the fact that it is cleared from their system more quickly.[2][7]

Esketamine has an affinity for the PCP binding site of the NMDA receptor 3-4 times higher than that of R(−)-ketamine. Unlike R(−)-ketamine, esketamine does not bind significantly to sigma receptors. Esketamine increases glucose metabolism in frontal cortex, while R(−)-ketamine decreases glucose metabolism in the brain. This difference may be responsible for the fact that esketamine generally has a more dissociative or hallucinogenic effect while R(−)-ketamine is reportedly more relaxing.[7] However, other studies have found no difference between the isomers in the patient's level of vigilance.[5]

Potential use as an antidepressant

Main article: Ketamine § Antidepressant use

Johnson & Johnson is developing a nasal spray formulation of esketamine as a treatment for depression in patients that have been unresponsive to other antidepressants in the United States.[1] As of July 2014, phase II clinical trials of intranasal esketamine sponsored by the Johnson & Johnson subsidiary Janssen Pharmaceutica are underway.[1][8] Other pharmaceutical companies are also developing new antidepressant drugs that act similarly to ketamine, including Naurex's rapastinel (GLYX-13) and NRX-1074, and Cerecor's CERC-301.[1]

Although most studies suggest that esketamine is preferable for medical uses, a 2013 study found that the antidepressant effect of R(−)-ketamine lasted longer than those of S(+)-ketamine in mice.[9]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 Wijesinghe, R (2014). "Emerging Therapies for Treatment Resistant Depression". Ment Health Clin. 4 (5): 56. ISSN 2168-9709.
  2. ↑ 2.0 2.1 PMID 9893910 (PMID 9893910)
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  3. ↑ PMID 11719729 (PMID 11719729)
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  4. ↑ PMID 10553955 (PMID 10553955)
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  5. ↑ 5.0 5.1 PMID 1443509 (PMID 1443509)
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  6. ↑ PMID 7840417 (PMID 7840417)
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  7. ↑ 7.0 7.1 PMID 9088882 (PMID 9088882)
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  8. ↑ http://clinicaltrials.gov/show/NCT01998958
  9. ↑ PMID 24316345 (PMID 24316345)
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