Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders
There is substantial evidence that cholinergic system function impairment plays a significant role in many central nervous system (CNS) disorders. During the past three decades, muscarinic receptors (mAChRs) have been implicated in various pathologies and have been prominent targets of drug-design e...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/2/398 |
| _version_ | 1797482400209436672 |
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| author | Chad R. Johnson Brian D. Kangas Emily M. Jutkiewicz Jack Bergman Andrew Coop |
| author_facet | Chad R. Johnson Brian D. Kangas Emily M. Jutkiewicz Jack Bergman Andrew Coop |
| author_sort | Chad R. Johnson |
| collection | DOAJ |
| description | There is substantial evidence that cholinergic system function impairment plays a significant role in many central nervous system (CNS) disorders. During the past three decades, muscarinic receptors (mAChRs) have been implicated in various pathologies and have been prominent targets of drug-design efforts. However, due to the high sequence homology of the orthosteric binding site, many drug candidates resulted in limited clinical success. Although several advances in treating peripheral pathologies have been achieved, targeting CNS pathologies remains challenging for researchers. Nevertheless, significant progress has been made in recent years to develop functionally selective orthosteric and allosteric ligands targeting the mAChRs with limited side effect profiles. This review highlights past efforts and focuses on recent advances in drug design targeting these receptors for Alzheimer’s disease (AD), schizophrenia (SZ), and depression. |
| first_indexed | 2024-03-09T22:31:48Z |
| format | Article |
| id | doaj.art-58219d084dc5447082d6c51a0191f535 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T22:31:48Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-58219d084dc5447082d6c51a0191f5352023-11-23T18:54:57ZengMDPI AGBiomedicines2227-90592022-02-0110239810.3390/biomedicines10020398Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System DisordersChad R. Johnson0Brian D. Kangas1Emily M. Jutkiewicz2Jack Bergman3Andrew Coop4Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Pharmacy Hall North Room 623, 20 N. Pine St., Baltimore, MD 21202, USABehavioral Biology Program, McLean Hospital, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USADepartment of Pharmacology, University of Michigan, 1150 W. Medical Center Dr., Ann Arbor, MI 48109, USABehavioral Biology Program, McLean Hospital, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USADepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Pharmacy Hall North Room 623, 20 N. Pine St., Baltimore, MD 21202, USAThere is substantial evidence that cholinergic system function impairment plays a significant role in many central nervous system (CNS) disorders. During the past three decades, muscarinic receptors (mAChRs) have been implicated in various pathologies and have been prominent targets of drug-design efforts. However, due to the high sequence homology of the orthosteric binding site, many drug candidates resulted in limited clinical success. Although several advances in treating peripheral pathologies have been achieved, targeting CNS pathologies remains challenging for researchers. Nevertheless, significant progress has been made in recent years to develop functionally selective orthosteric and allosteric ligands targeting the mAChRs with limited side effect profiles. This review highlights past efforts and focuses on recent advances in drug design targeting these receptors for Alzheimer’s disease (AD), schizophrenia (SZ), and depression.https://www.mdpi.com/2227-9059/10/2/398Alzheimer’s diseaseschizophreniadepressionmajor depressive disorderdrug designmuscarinic receptors |
| spellingShingle | Chad R. Johnson Brian D. Kangas Emily M. Jutkiewicz Jack Bergman Andrew Coop Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders Biomedicines Alzheimer’s disease schizophrenia depression major depressive disorder drug design muscarinic receptors |
| title | Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders |
| title_full | Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders |
| title_fullStr | Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders |
| title_full_unstemmed | Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders |
| title_short | Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders |
| title_sort | drug design targeting the muscarinic receptors and the implications in central nervous system disorders |
| topic | Alzheimer’s disease schizophrenia depression major depressive disorder drug design muscarinic receptors |
| url | https://www.mdpi.com/2227-9059/10/2/398 |
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