五羟色胺1A受体
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5-HT1A受体 5-HT1A Receptors in Psychopharmacology
科室：神经内三科
I General features
II Location
III
Mechanism
IV Function
Ⅴ Drugs
Ⅵ References
I General features
14 serotonin (5-HT) receptors that can be subdivided into 7 classes [1].
1. Schatzberg AF, Nemeroff CB. The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Ed. Apr 2009, American Psychiatric Publishing Inc.
properties. 7. Nash JR, Sargent PA, Rabiner EA, et al. Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study. Br J
2010;11(7):802-12.
多谢聆听
4. Kalia R, Mittal M S, and Preskorn S H:Vilazodone for major depressive disorder. Current Psychiatry. 2011;10(4): 84-88. 5. Rang H, Ritter J. Dale M, et al. Pharmacology. 3rd Ed. Churchill Livingstone, UK. 6. Newman-Tancredi A, Kleven MS. Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor
3. Newman-Tancredi. Biased agonism at serotonin 5-HT1A receptors: preferential postsynaptic activity for improved therapy of CNS disorders. Neuropsychiatry. 2011;1(2):149-164.
Depression
Overexpression
Anxiety
Depression
源自文库
Auto- and Heteroreceptors
Elevated Lower
-
Diminished [丁螺环酮， 曲唑酮] -
Autoreceptors
Elevated No impact
Diminished [13,116,117]
Ⅲ Function
Ⅳ Drugs
azapirone
坦度螺酮为5-HT1A受体部分激动 剂，
对突触后膜的5-HT1A受体激动作用 仅为5-HT的60％。
因而不会使神经活动受到完全的抑 制或兴奋。
事实上，该药对5-HT系统的调节， 更像是发挥着一种“5-HT系统稳定 剂”的作用。
I References
Location ：presynaptic and postsynaptic regions Function：anxiolytic, antidepressant and antipsychotic
medications
I Location
Presynaptic autoreceptors
On serotonergic cell bodies in the raphe nuclei. Upon stimulation, inhibit the firing of 5-HT neurons [3,4]
Abundant 5-HT1A receptors are also expressed on astrocytes and other glia where they are thought to be involved in mood control [1].
Ⅱ Mechanism
Blue dots—serotonin, red shape—SERT, green shape—5-HT1A receptor
2. Drago A, Ronchi DD, Serretti A. 5-HT1A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies. Int J Neuropsychopharmacol. 2008;11(5):701-21.
Psychiatry. 2008 Sep;193(3):229-34. 8. Lesch KP, Wiesmann M, Hoh A, et al. 5-HT1A receptor-effector system responsivity in panic disorder. Psychopharmacology (Berl). 1992;106(1):111-7. 9. Neumeister A, Bain E, Nugent AC, et al. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci. 2004;24(3):589-91. 10. Savitz J, Lucki I, Drevets WC. 5-HT(1A) receptor function in major depressive disorder. Prog Neurobiol. 2009;88(1):17-31. 11. Newman-Tancredi. The importance of 5-HT1A receptor agonism in antipsychotic drug action: rationale and perspectives. Curr Opin Investig Drugs.
5-HT1A receptors are G-protein coupled receptors
exert their effects through Gi/o proteins to inhibit adenylyl cyclase, and other second messenger cascades such as MAPK pathways and NMDA receptor channels [2].
5-HT1A heteroreceptors reduce the activity of the pyramidal neurons while 5-HT2A receptors activate the neurons.
Ⅲ Function
Behavioural Effect
Whole life knockout Anxiety Depression Reduced activity Anxiety
Elevated [110]
Heteroreceptors
No impact Elevated Elevated [115] -
-
13. Richardson-Jones J.W., Craige C.P., Guiard B.P., Stephen A., Metzger K.L., Kung H.F., Gardier A.M., Dranovsky A., David D.J., Beck S.G., et al. 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron. 2010;65:40–52. [PMC free article] [PubMed] [Google Scholar] 14. Garcia-Garcia A.L., Newman-Tancredi A., Leonardo E.D. 5-HT (1A) receptors in mood and anxiety: Recent insights into autoreceptor versus heteroreceptor function. Psychopharmacology. 2014;231:623–636. [PMC free article] [PubMed] [Google Scholar]
Postsynaptic heteroreceptors
In the limbic system, including the hippocampus, septum, amygdala and entorhinal cortex as well as the hypothalamus, cortex and dorsal horn [1,3,5]
科室：神经内三科
I General features
II Location
III
Mechanism
IV Function
Ⅴ Drugs
Ⅵ References
I General features
14 serotonin (5-HT) receptors that can be subdivided into 7 classes [1].
1. Schatzberg AF, Nemeroff CB. The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Ed. Apr 2009, American Psychiatric Publishing Inc.
properties. 7. Nash JR, Sargent PA, Rabiner EA, et al. Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study. Br J
2010;11(7):802-12.
多谢聆听
4. Kalia R, Mittal M S, and Preskorn S H:Vilazodone for major depressive disorder. Current Psychiatry. 2011;10(4): 84-88. 5. Rang H, Ritter J. Dale M, et al. Pharmacology. 3rd Ed. Churchill Livingstone, UK. 6. Newman-Tancredi A, Kleven MS. Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor
3. Newman-Tancredi. Biased agonism at serotonin 5-HT1A receptors: preferential postsynaptic activity for improved therapy of CNS disorders. Neuropsychiatry. 2011;1(2):149-164.
Depression
Overexpression
Anxiety
Depression
源自文库
Auto- and Heteroreceptors
Elevated Lower
-
Diminished [丁螺环酮， 曲唑酮] -
Autoreceptors
Elevated No impact
Diminished [13,116,117]
Ⅲ Function
Ⅳ Drugs
azapirone
坦度螺酮为5-HT1A受体部分激动 剂，
对突触后膜的5-HT1A受体激动作用 仅为5-HT的60％。
因而不会使神经活动受到完全的抑 制或兴奋。
事实上，该药对5-HT系统的调节， 更像是发挥着一种“5-HT系统稳定 剂”的作用。
I References
Location ：presynaptic and postsynaptic regions Function：anxiolytic, antidepressant and antipsychotic
medications
I Location
Presynaptic autoreceptors
On serotonergic cell bodies in the raphe nuclei. Upon stimulation, inhibit the firing of 5-HT neurons [3,4]
Abundant 5-HT1A receptors are also expressed on astrocytes and other glia where they are thought to be involved in mood control [1].
Ⅱ Mechanism
Blue dots—serotonin, red shape—SERT, green shape—5-HT1A receptor
2. Drago A, Ronchi DD, Serretti A. 5-HT1A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies. Int J Neuropsychopharmacol. 2008;11(5):701-21.
Psychiatry. 2008 Sep;193(3):229-34. 8. Lesch KP, Wiesmann M, Hoh A, et al. 5-HT1A receptor-effector system responsivity in panic disorder. Psychopharmacology (Berl). 1992;106(1):111-7. 9. Neumeister A, Bain E, Nugent AC, et al. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci. 2004;24(3):589-91. 10. Savitz J, Lucki I, Drevets WC. 5-HT(1A) receptor function in major depressive disorder. Prog Neurobiol. 2009;88(1):17-31. 11. Newman-Tancredi. The importance of 5-HT1A receptor agonism in antipsychotic drug action: rationale and perspectives. Curr Opin Investig Drugs.
5-HT1A receptors are G-protein coupled receptors
exert their effects through Gi/o proteins to inhibit adenylyl cyclase, and other second messenger cascades such as MAPK pathways and NMDA receptor channels [2].
5-HT1A heteroreceptors reduce the activity of the pyramidal neurons while 5-HT2A receptors activate the neurons.
Ⅲ Function
Behavioural Effect
Whole life knockout Anxiety Depression Reduced activity Anxiety
Elevated [110]
Heteroreceptors
No impact Elevated Elevated [115] -
-
13. Richardson-Jones J.W., Craige C.P., Guiard B.P., Stephen A., Metzger K.L., Kung H.F., Gardier A.M., Dranovsky A., David D.J., Beck S.G., et al. 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron. 2010;65:40–52. [PMC free article] [PubMed] [Google Scholar] 14. Garcia-Garcia A.L., Newman-Tancredi A., Leonardo E.D. 5-HT (1A) receptors in mood and anxiety: Recent insights into autoreceptor versus heteroreceptor function. Psychopharmacology. 2014;231:623–636. [PMC free article] [PubMed] [Google Scholar]
Postsynaptic heteroreceptors
In the limbic system, including the hippocampus, septum, amygdala and entorhinal cortex as well as the hypothalamus, cortex and dorsal horn [1,3,5]