Serotonin

Information about Serotonin

Published on July 14, 2014

Author: NischalTyagi

Source: authorstream.com

Content

SEROTONIN- happy hormone : SEROTONIN - happy hormone Efforts By: Nischal Tyagi Introduction: Introduction Serotonin – 5-hydroxytryptamine (5-HT) is an ubiquitary monoamine acting as one of the neurotransmitters at synapses of nerve cells. It has a similar chemical structure with tryptamine,dimethyltryptamine,melatonin and bufothein belonging to the group of indolalkylamins Introduction: Introduction Its role is expected in the etiology of several diseases, including depression, schizophrenia, anxiety and panic disorders, migraine, hypertension, pulmonary hypertension,eating disorders, vomiting and irritable bowel syndromes. History of Serotonin: History of Serotonin Serotonin was discovered in the late 1940s and within a next decade, there were indications for its existence in the central nervous system of animals and its neurotransmitter function. By the late 1950s, evidence for 5-HT receptor heterogeneity was found in the periphery and in 1979, two distinct populations of 5-HT binding sites were identified in rat brain: 5-HT1 and 5-HT2 sites Biosynthesis of Serotonin: Biosynthesis of Serotonin Biosynthesis of serotonin begins with hydroxylation of an essential amino acid L-tryptophan. L-tryptophan is transported through the blood-brain barrier into the brain using the amino acids transmitters. Tryptophanhydroxylase is the speed limiting step of 5-HT synthesis. This enzyme is found in the brain only in the serotoninergic neurons. It enables conversion of tryptophan into 5-hydroxytryptophan, followed by the decarbolization mediated by aromatic L-amino acid decarboxylase onto 5-hydroxytryptamine Biosynthesis of Serotonin: Biosynthesis of Serotonin The serotonergic neuron: The serotonergic neuron Deactivation and Breakdown: Deactivation and Breakdown Action terminated by active re-uptake process into neurons and ganglia. Then broken down by MAO. MAO-A is more selective for serotonin oxidation by being able to metabolise serotonin than MAO-B. MAO breaks down 5HT into several things such as 5-hydrozindoleacetic acid (5HIAA) Inhibition of MAO-A activity to prevent serotonin metabolism in the CNS has been linked to the antidepressant properties Effect on organs and tissues: : Effect on organs and tissues: Nervous system : Serotonin acts as a neurotransmitter 5HT3 receptors in the medullary vomiting centre and in the GIT participate in vomiting reflex. Serotonin is a potent stimulant of pain and itching and it is involved in some of pain-associated insect or plantstings . Effect on organs and tissues: Effect on organs and tissues Air ways: Serotonin has a small direct stimulant effect on smooth muscle of bronchi However, high levels of serotonin found in carcinoid tumour results in episodes of bronchoconstriction . PowerPoint Presentation: Cardiovascular system : Serotonin has a direct vasoconstriction effect on vascular smooth muscle (mediated through 5HT2) It causes vasodilatation of blood vessels of skeletal muscle and the heart. Serotonin causes platelets aggregation. Gastrointestinal tract: contraction of GIT smooth muscle facilitating peristalsis (5HT2 receptors). Effect on organs and tissues Serotonin Receptors: Serotonin Receptors receptor 5HT1 5HT2 5HT3 5HT4 5HT5 5HT6 5HT7 subtype 5HT1A, 5HT1B, 5HT1D, 5HT1E, 5HT1F 5HT2A, 5HT2B, 5HT2C     5HT3A, 5HT3B   5HT1A, 5HT1B     major signaling pathway cAMP↓ IP3  ion channel cAMP  cAMP? cAMP  cAMP  PowerPoint Presentation: Receptor Effects and functions Agonists Antagonists 5-HT1A CNS : Aggression, Anxiety, Addiction, Appetite,Emesis , Sleep,Memory , Mood, Nausea, Respiration. Cardiovascular system : Blood pressure, Heart rate, Vasoconstriction, Penile erection Other : Pupil dilation buspiron , dihydroergotamine , eltoprazine , ergotamine, tandospirone , urapidil , yohimbine oxprenolol , pindolol , Propanolol , spiperone , alprenolol , asenapine , cyanopindolol PowerPoint Presentation: Receptor Effects and functions Agonists Antagonists 5-HT1B CNS: Aggression, Anxiety, Learning, Addiction, Locomotion, Memory, Mood, Sexual behavior Vessels: Pulmonary vasoconstriction, Penile erection dihydroergotamine , eletriptan , eltoprazine , ergotamine, methysergide , sumatriptan yohimbine , alprenolol , asenapine , cyanopindolol , pindolol , propanolol 5-HT1D CNS: Locomotion, Anxiety Vessels: Cerebral vasoconstriction sumatriptan , almotriptan , dihydroergotamine , eletriptan , ergotamine, frovatriptan , methysergide ketanserin , metergoline , methiothepin , Rauwolscine , ritanserin PowerPoint Presentation: Receptor Effect & Functions Agonists Antagonists 5-HT1F Blood Vessels : Vasoconstriction CNS: Locomotion, Anxiety eletriptan , naratriptan , sumatriptan methiothepin 5-HT2A CNS: Anxiety, Appetite, Addiction, Cognition, Imagination, Learning, Memory, Mood, Perception, Sexual behavior, Sleep, Thermoregulation Smooth muscles: Contraction Vessels: Vasoconstriction, Vasodilation Platelets: Aggregation bufotenin , ergonovine , lisuride , LSD (in CNS),mescaline, myristicin,psilocin aripiprazole , clozapine , cyproheptadine , eplivanserin, etoperidone , iloperidone,ketanserin , methysergide , mirtazapine,nefazodone,olanzapine , quetiapine , risperidone , PowerPoint Presentation: Receptor Effect & Function Agonists Antagonists 5-HT2B CNS: Anxiety , Appetite, Sleep Gastrointestinal tract : GI motility Vessels : Vasoconstriction Cardiovascular system : Cardiovascular function α- metyl-5-HT, fenfluramine , LSD(in CNS), norfenfluramine agomelatine , asenapine,ketanserin , LSD(PNS), methysergide , ritanserin,tegaserod , yohimbine 5-HT2C CNS: Anxiety, Appetite, Addiction, Locomotion , Mood, Sexual behaviour , Sleep,Thermoregulation Gastrointestinal tract : GI motility Vessels: Vasoconstriction, Penile erection α- metyl-5-HT, aripiprazole , ergonovine , lorcaserin , LSD (in CNS) clozapine , cyproheptadine , eltoprazine , etoperidone , fluoxetine,ketanserin , lisuride , LSD(in PNS), methysergide , mianserin,mirtazapine 5-HT3 (5-HT3A, 5-HT3B) CNS, PNS: Anxiety, Addiction, Anxiety, Nausea, Emesis, Learning, Memory Gastrointestinal tract: GI motility, Nausea, Emesis α- metyl-5-HT, quipazine alosetron , clozapine , dolasetron , granisetron , memantine , metoclopramide , mianserin , mirtazapine , olanzapine , ondansetron , quetiapine , tropisetron PowerPoint Presentation: Receptor Effect & Function Agonists Antagonists 5-HT4 (5-HT4A-H) CNS: Anxiety: Appetite, Learning, Memory, Mood, Respiration Gastrointestinal tract: GI motility cisapride , metoclopramide,mosapride , prucalopride , renzapride , tegaserod , Zacopride L-lysine, piboserod 5-HT5 (only 5-HT5A receptor in humans) CNS: Locomotion, Sleep ergotamine, valerenic acid asenapine , dimebolin , methiothepin , ritanserin 5-HT6 CNS: Anxiety, Cognition: Learning , Memory: Mood EMD-386.088, EMDT aripiprazole , asenapine , clozapine , dimebolin , iloperidone , olanzapine 5-HT7 CNS: Anxiety, Memory, Mood, Respiration , Sleep, Thermoregulation Vessels: Vasoconstriction 5-carboxytryptami n, LSD aripiprazole , asenapine , clozapine , iloperidone , ketanserin , metiotepín , olanzapine , ritanserin Drugs used to treat depressive disorders:: Drugs used to treat depressive disorders: Action of an SSRI: Action of an SSRI Serotonin Syndrome: Serotonin Syndrome Toxic, potentially fatal effects require a combination of serotonergic agents, such as an SSRI with an MAOI. Symptoms: euphoria, drowsiness, sustained rapid eye movement, overreaction of reflexes, rapid muscle contraction, abnormal movements of the foot, drunk, dizzy feeling, high body temperature, shivering , diarrhea ,loss of consciousness, death Serotonin Syndrome: Serotonin Syndrome Conclusion: Conclusion Serotonin is unique among the monoamines in that its effects are subserved by distinct G-protein-coupled receptors and one ligand-gated ion channel. The diversity in receptors described above suggests that under physiological and pathological conditions the status of the receptors may vary from one patient to another References: References Serotonin Receptors – From Molecular Biology to ClinicalApplications By - M. PYTLIAK,V. VARGOVÁ, V. MECHÍROVÁ,M. FELŠÖCl 5-Hydroxytryptamine Dr. Jawad H. Ahmed, Department of Pharmacology, 2009 THANKS: THANKS

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