Is the History Repeated? Can (2,6)-Hydroxynorketamine be Another Antidepressant?
Historically, identification of active metabolites has contributed to drug discovery for psychiatric disorders. It has led to the identification of new medications such as desipramine (a metabolite of imipramine) and paliperidone (a metabolite of risperidone). ( R,S )-Ketamine, which has been regard...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2018-12-01
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| Series: | Journal of Experimental Neuroscience |
| Online Access: | https://doi.org/10.1177/1179069518815445 |
| _version_ | 1818576250124369920 |
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| author | Shigeyuki Chaki Jun-ichi Yamaguchi |
| author_facet | Shigeyuki Chaki Jun-ichi Yamaguchi |
| author_sort | Shigeyuki Chaki |
| collection | DOAJ |
| description | Historically, identification of active metabolites has contributed to drug discovery for psychiatric disorders. It has led to the identification of new medications such as desipramine (a metabolite of imipramine) and paliperidone (a metabolite of risperidone). ( R,S )-Ketamine, which has been regarded as the greatest breakthrough in depression research, is rapidly and stereoselectively metabolized into a variety of metabolites. Therefore, identification of an active substance after administration of ( R,S )-ketamine is a critical issue, not only to delineate the underlying mechanisms but also to pave the way to develop a new antidepressant. Recently, one of the metabolites of ( R,S )-ketamine, namely, (2 R ,6 R )-hydroxynorketamine (HNK) was proposed as an active metabolite formed after administration of ( R,S )-ketamine, and even as being essential for ( R,S )-ketamine to exert its antidepressant effects. However, this is still controversial. Indeed, we demonstrated that the antidepressant effect of (2 R ,6 R )-HNK is not as potent as that of its parent compounds (( R )-ketamine and ( R,S )-ketamine), and that (2 R ,6 R )-HNK is not essential for ( R )-ketamine to exert its antidepressant effects. From the historical point of view, however, there is potential to discover new medications by further investigations of (2 R ,6 R )-HNK. Therefore, more careful and thorough investigation of (2 R ,6 R )-HNK is needed for the discovery of more efficacious and safer antidepressants. |
| first_indexed | 2024-12-16T06:11:02Z |
| format | Article |
| id | doaj.art-3d90d0f4684241b7bc2061f0b8eb9b19 |
| institution | Directory Open Access Journal |
| issn | 1179-0695 |
| language | English |
| last_indexed | 2024-12-16T06:11:02Z |
| publishDate | 2018-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Experimental Neuroscience |
| spelling | doaj.art-3d90d0f4684241b7bc2061f0b8eb9b192022-12-21T22:41:23ZengSAGE PublishingJournal of Experimental Neuroscience1179-06952018-12-011210.1177/1179069518815445Is the History Repeated? Can (2,6)-Hydroxynorketamine be Another Antidepressant?Shigeyuki ChakiJun-ichi YamaguchiHistorically, identification of active metabolites has contributed to drug discovery for psychiatric disorders. It has led to the identification of new medications such as desipramine (a metabolite of imipramine) and paliperidone (a metabolite of risperidone). ( R,S )-Ketamine, which has been regarded as the greatest breakthrough in depression research, is rapidly and stereoselectively metabolized into a variety of metabolites. Therefore, identification of an active substance after administration of ( R,S )-ketamine is a critical issue, not only to delineate the underlying mechanisms but also to pave the way to develop a new antidepressant. Recently, one of the metabolites of ( R,S )-ketamine, namely, (2 R ,6 R )-hydroxynorketamine (HNK) was proposed as an active metabolite formed after administration of ( R,S )-ketamine, and even as being essential for ( R,S )-ketamine to exert its antidepressant effects. However, this is still controversial. Indeed, we demonstrated that the antidepressant effect of (2 R ,6 R )-HNK is not as potent as that of its parent compounds (( R )-ketamine and ( R,S )-ketamine), and that (2 R ,6 R )-HNK is not essential for ( R )-ketamine to exert its antidepressant effects. From the historical point of view, however, there is potential to discover new medications by further investigations of (2 R ,6 R )-HNK. Therefore, more careful and thorough investigation of (2 R ,6 R )-HNK is needed for the discovery of more efficacious and safer antidepressants.https://doi.org/10.1177/1179069518815445 |
| spellingShingle | Shigeyuki Chaki Jun-ichi Yamaguchi Is the History Repeated? Can (2,6)-Hydroxynorketamine be Another Antidepressant? Journal of Experimental Neuroscience |
| title | Is the History Repeated? Can (2,6)-Hydroxynorketamine be Another Antidepressant? |
| title_full | Is the History Repeated? Can (2,6)-Hydroxynorketamine be Another Antidepressant? |
| title_fullStr | Is the History Repeated? Can (2,6)-Hydroxynorketamine be Another Antidepressant? |
| title_full_unstemmed | Is the History Repeated? Can (2,6)-Hydroxynorketamine be Another Antidepressant? |
| title_short | Is the History Repeated? Can (2,6)-Hydroxynorketamine be Another Antidepressant? |
| title_sort | is the history repeated can 2 6 hydroxynorketamine be another antidepressant |
| url | https://doi.org/10.1177/1179069518815445 |
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