Abstract
challenges associated with developing more effective treatments for neurologic and psychiatric illness such as Alzheimer's disease and schizophrenia are considerable. Both the symptoms and the pathophysiology of these conditions are complex and poorly understood and the clinical presentations across different patients can be very heterogeneous. Moreover, it has become apparent that the reductionist approach to drug discovery for these illnesses that has dominated the field for decades (i.e., the development of highly selective compounds or other treatment modalities focused on a very specific pathophysiologic target) has not been widely successful. Accordingly, a variety of new strategies have emerged including the development of "multitarget-directed ligands" (MTDLs), the development and/or identification of compounds that exhibit "multifunctional" activity (e.g., pro-cognitive plus neuroprotective, pro-cognitive plus antipsychotic activity), "repurposing" strategies for existing compounds that have other clinical indications, and novel "adjunctive" treatment strategies that might enhance the efficacy of the currently available treatments. Interestingly, a variety of ligands at nicotinic acetylcholine receptors (nAChRs) appear to have the potential to fulfill one or more of these desirable properties (i.e., multifunctional, repurposing, or adjunctive treatment potential). The purpose of this review (while not all-inclusive) is to provide an overview of a variety of nAChR ligands that demonstrate potential in these categories, particularly, "multifunctional" properties. Due to their densities in the mammalian brain and the amount of literature available, the review will focus on ligands of the high affinity α4β2 nAChR and the low affinity α7 nAChR.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 388-398 |
| Number of pages | 11 |
| Journal | Biochemical Pharmacology |
| Volume | 97 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 15 2015 |
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Keywords
- 's disease
- Alzheimer
- Cholinergic
- Memory
- Mild Cognitive Impairment
- Schizophrenia
ASJC Scopus subject areas
- Biochemistry
- Pharmacology
Cite this
Nicotinic ligands as multifunctional agents for the treatment of neuropsychiatric disorders. / Terry, Alvin V; Callahan, Patrick Michael; Hernandez, Caterina M.
In: Biochemical Pharmacology, Vol. 97, No. 4, 15.10.2015, p. 388-398.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Nicotinic ligands as multifunctional agents for the treatment of neuropsychiatric disorders
AU - Terry, Alvin V
AU - Callahan, Patrick Michael
AU - Hernandez, Caterina M.
PY - 2015/10/15
Y1 - 2015/10/15
N2 - challenges associated with developing more effective treatments for neurologic and psychiatric illness such as Alzheimer's disease and schizophrenia are considerable. Both the symptoms and the pathophysiology of these conditions are complex and poorly understood and the clinical presentations across different patients can be very heterogeneous. Moreover, it has become apparent that the reductionist approach to drug discovery for these illnesses that has dominated the field for decades (i.e., the development of highly selective compounds or other treatment modalities focused on a very specific pathophysiologic target) has not been widely successful. Accordingly, a variety of new strategies have emerged including the development of "multitarget-directed ligands" (MTDLs), the development and/or identification of compounds that exhibit "multifunctional" activity (e.g., pro-cognitive plus neuroprotective, pro-cognitive plus antipsychotic activity), "repurposing" strategies for existing compounds that have other clinical indications, and novel "adjunctive" treatment strategies that might enhance the efficacy of the currently available treatments. Interestingly, a variety of ligands at nicotinic acetylcholine receptors (nAChRs) appear to have the potential to fulfill one or more of these desirable properties (i.e., multifunctional, repurposing, or adjunctive treatment potential). The purpose of this review (while not all-inclusive) is to provide an overview of a variety of nAChR ligands that demonstrate potential in these categories, particularly, "multifunctional" properties. Due to their densities in the mammalian brain and the amount of literature available, the review will focus on ligands of the high affinity α4β2 nAChR and the low affinity α7 nAChR.
AB - challenges associated with developing more effective treatments for neurologic and psychiatric illness such as Alzheimer's disease and schizophrenia are considerable. Both the symptoms and the pathophysiology of these conditions are complex and poorly understood and the clinical presentations across different patients can be very heterogeneous. Moreover, it has become apparent that the reductionist approach to drug discovery for these illnesses that has dominated the field for decades (i.e., the development of highly selective compounds or other treatment modalities focused on a very specific pathophysiologic target) has not been widely successful. Accordingly, a variety of new strategies have emerged including the development of "multitarget-directed ligands" (MTDLs), the development and/or identification of compounds that exhibit "multifunctional" activity (e.g., pro-cognitive plus neuroprotective, pro-cognitive plus antipsychotic activity), "repurposing" strategies for existing compounds that have other clinical indications, and novel "adjunctive" treatment strategies that might enhance the efficacy of the currently available treatments. Interestingly, a variety of ligands at nicotinic acetylcholine receptors (nAChRs) appear to have the potential to fulfill one or more of these desirable properties (i.e., multifunctional, repurposing, or adjunctive treatment potential). The purpose of this review (while not all-inclusive) is to provide an overview of a variety of nAChR ligands that demonstrate potential in these categories, particularly, "multifunctional" properties. Due to their densities in the mammalian brain and the amount of literature available, the review will focus on ligands of the high affinity α4β2 nAChR and the low affinity α7 nAChR.
KW - 's disease
KW - Alzheimer
KW - Cholinergic
KW - Memory
KW - Mild Cognitive Impairment
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84943357229&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943357229&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2015.07.027
DO - 10.1016/j.bcp.2015.07.027
M3 - Review article
VL - 97
SP - 388
EP - 398
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 4
ER -