Fig. 1. Structural relationships of the various indolealkyl amin Compound Substitutions Tryptamine R1 and R2H Serotoinin Tryptamine with 5 hydroxy DMT

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1 KISEP Special Articles 생물정신의학 Vol. 4, No. 2, December 1997 세로토닌과정신의학 양병환 * Serotonin in Psychiatry ByungHwan Yang, M.D., Ph.D.* ABSTRACT S erotonin has been implicated in the etiology of many disease states and may be particularly important mental illness, such as depression, anxiety, schizophrenia, sleep disorders, suicide, eating disorders, obsessive compulsive disorders, migraine and others. Many currently used treatments of these disorders are thought to act by modulating serotonergic function. The identification of many serotonin subtypes, most of which have been shown to have functional activity and differential distribution, has stimulated considerable effort into synthesizing selective ligandsdrugs to help understand their significance. This should understand the role of serotonin in mental disorders and these new drugs can be studied alone and in combination with other treatments in order to clarify the parameters of drug use for the clinical effect. KEY WORDSSerotoninMental disorderserotonin receptor subtypesselective serotonin receptor drugs. 서 론 Department of Neuropsychiatry, College of Medicine the Mental Health Research Institute, Hanyang University, Seoul, Korea

2 Fig. 1. Structural relationships of the various indolealkyl amin Compound Substitutions Tryptamine R1 and R2H Serotoinin Tryptamine with 5 hydroxy DMT* R1 and R2methyl DET* R1 and R2ethyl Bufotenine* 5 hydroxy, DMT Szara psychotrope* 6 hydroxy, DET Psilocin* 4 hydroxy, DMT Harmaline* 6 methoxyr1 forms isopropyl link to C2 5-MT 5-methoxytryptamine 5, 6 DHT 5,6 dihydroxytryptamine 5, 7 DHT 5,7 dihydroxytryptamine *Pychotropic or behavioral effects 세로토닌계 Fig. 2. The metabolic pathways available for the synthesis and metabolism of serotoin

3 Fig. 3. Serotonergic pathways. 세로토닌과행동 (Behavior) Table 1. Clinical areas influenced by altered 5-HT function Affective disorders Substance abuse Anxiety disorders Pain sensitivity Obsessive-compulsive Emesis disorder Mycoclonis Schizophrenia Neuroendocrine regulation Eating disorders Circadian rhythm regulation Sleep disorders Stress disorders Sexual disorders Carcinoid syndrome Impulse disorders Developmental disorders Aging and neurodegenerative disorders Fig. 4. Influence of some serotonergic dimensions on diagnosis. AbbreviationsOCDobsessive compulsive disorder. PTSDposttraumatic stress disorder

4 세로토닌수용체아형 Table 2. Serotonin receptor chassification Effector Primary Subtype mechanism effector Brain locations 5-HT1A AC, K chanel Hippocampus, amygdalal, entorhinal cortex, raphe nuclei 5-HT1B AC Hippocampus, striatum, substantia nigra, rapha nuclei, cerebellum 5-HT1D AC Dorsal raphe nucleus 5-HT1D AC Hippocampus, striatum, substantia nigra, raphe nuclei, cerebellum 5-HT1E AC Cerebral cortex, putamen G protein coupled 5-HT1F AC Cerebral cortex, hippocampus, raphe nuclei, solitary tract nucleus 5-HT2A PI turnover Cerbral cortex, hippocampus, striatum 5-HT2B PI turnover Stomach fundus 5-HT2C PI turnover Choroid plexus, hippocampus, habenula, substantia nigra, locus coreruleus, raphe nuclei 5-HT4 AC Colliculi, hippocampus 5-HT5A Unknown Olfactory bulb, cerebral cortex, hippocampus, habenula, cerebellum 5-HT5B Unknown Hippocampus, habenula, raphe nuclei 5-HT6 AC Striatum, amygdala, cortex 5-HT7 AC Thalamus, hypothalamus Ligand-gated 5-HT3 ion channel Cation selective excitatory Olfactory bulb, cerebral cortex, hippocampus, amygdala, hypothalamus, solitary tract nucleus Note. ACadenylate cyclase activity PIphosphatidylinositol

5 Fig. 5. A schematic diagram of aspects of serotonergic neurotransmission that could be modified by pharmacologic treatments or that may be altered in disease states. 세로토닌과임상장애

6 결어 중심단어 : 참고문헌 Baker KG, Halliday GM, Toerk I(1990):Cytoarchitecture of the human dorsal raphe nucleus. J Comp Neurol 301: Conn PJ, Sanders-Bush E(1986):Serotonin stimulated phosphoinositide turnover. J Pharmacol Exp Ther 234: Derkach V, Suprenant A, North RA(1989):5-HT3 receptors are membrane ion channels. Nature 339: Dubovsky SL(1994):Beyond the serotonin reuptake inhibitors. J Clin Psychiatry 55-2, Suppl Dubovsky SL, Thomas M(1995):Serotonergic mechanisms and current and future psychiatric practice. J Clin Psychiatry 56, Suppl 2, Dulawa SC, Scearce-Levie RHK, Geyer MA(1997):Serotonin1B receptor modulation of startle reactivity, habituation, and prepulse inhibition in wild-type and serotonin1b knockout mice. Psychopharmacology 132: Fargin A, RaymondJ, Lohie J Koblika BK, Caron MJ, Lefkowwitz RJ(1988):The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-ht1A receptor. Nature 335: Foguet M, Hoyer D, Pardo LA(1990):Cloning and functional cha

7 racterization of the rat stomach fundus serotonin receptor. EMBO J 11: Gaddum J, Picarelli Z(1957):Two kinds of tryptamine receptor. British Journal of Pharmacology and chemotherapy 12: Glennon RA(1990):Do hallucinogens act as 5-HT2 agonists or antagonists? Neuropsychopharmacology 56: Grossman CJ, Kilpatrick GJ, Brunce KJ, Oxford AW, Gale JD, Whitehead JF, Hamphery PA(1993):Development of a radioligand binding assay for 5-HT4 receptors in guinea pig and rat brain. Br J Pharmacol 109: Hoyer D, Clarke DE, Fozard JR(1994):International union of pharmacology classification of receptors for serotonin. Pharmacol Rev 46: Hoyer D, Pazos A, Probst A(1986):Serotonin receptors in the human brain. Brain Res 376: Jalius D, MacDermott AB, Axel R(1988):Molecular charecterization of a functional cdna encoding the serotonin 1c receptor. Science 241: Levy FO, Gudermann T, Birnbaumer M, Kaumann AJ, Birnbaumer L(1992):Molecular cloning of a human gene encoding. a novel serotonin receptor mediating inhibition of adenylyl cyclas. FEBS Lett 296: Lidov HGQ, Molliver ME(1982):An immunohistochemical study of serotonin neuron development in the rat. Brain Ros Ball 8: Maricg AV, Peterson AS, Brake AJ, Meyers Rm, Julian D(1991): Primary structure and Functional expression of the 5-HT3 receptor:science 254: Meltzer HY, Matsubara S, Lee JC(1989):Classification of typical and atypical antipsychotic drugs on the basis of dopamin D-1, D2, and serotonin2. J Pharmacol Exp Ther 251: Meltzer HY, Nash TF(1991):Effects of antipsychotic drugs on serotonin receptors. Pharmacol Rev 43: Page IH(1952):The vascular action of natural serotonin, 5- and 7- hydroxytryptamine. J Pharmacol Exp Ther 105:58 Pazos A, Palacios JM(1985):Quantitative autoradiographic mapping of serotonin receptors in the rat brain. Brain Res 346: Pedigo N, Yamamura H, Nelson D(1981):Discrimination of multiple 3H 5-HT binding sites by the neuroleptic spiperone in rat brain. J Neurochem 36: Peorutka S, Snyder S(1979):Multiple serotonin receptors. Mol Pharmacol 16: Pompeiano M, Palacios JM, Mengod G(1994):Distribution of the serotonin 5-HT2 receptor subfamily mrnas. Molecular Brain Research 23: Roth BL, Crigo SC, Choudhary MS(1994):Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydrozytryptamine-7 receptors. J Pharmacol Exp Ther 268: Tecott LH, Julias DJ(1993):A new wave of serotonin receptors. Current Opinion in Neurobiology 3: Tecott L, Maricq A, Julius D(1993):Nervous system distribution of serotonin 5-HT3 receptor MRNA. Proc Natl Aca Sci USA 90: Whitaker-Azmitia PM, Claeke C, Azmitia EC(1993):5-HT1A immunoreactivity in brain astrocytes colocalized with GFAP. Synapse 14:

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