Indoleamines Lisham Ashrafioun Michele San GeorgeSlide 2
Melatonin vivo.colostate.eduSlide 3
Melatonin Receptors (ML1A) CNS areas SCN (organic clock) Anterior pituitary (occasional rearing) PNS areas Retina - circadian and conceptive reactions Cardiovascular framework - caudal conduit that potentiates NE-initiated constriction Reproductive framework – ovaries Immune framework – T cells Kidneys – Na maintenance GI Tract – unwinds smooth muscles (melatonin-5-HT criticism)Slide 4
Serotonin 5-Hydroxytryptamine (5-HT)Slide 5
Synthesis Tryptophan 5-Hydroxytrophan (5-HTP) Hydroxylase Amino Acid 5-Hydroxytryptamine (5-HT) DecarboxylaseSlide 6
Metabolism Monoamine 5-HT 5-HIAA Oxidase 5-HIAA: 5-Hydroxy indole amine corrosiveSlide 7
Inactivation-5HT reuptakeSlide 8
Distribution(PNS) Majority discharged from gut Responsible for smooth muscle compressions Release animated by sustenance admission Inhibits arrival of gastric corrosive Softens stool Cardiovascular framework – vasoconstrictor/vasodilator of vessels Bonchioconstriction Uterine withdrawalsSlide 9
Distribution: rat (Cooper, Bloom, Roth, 2003)Slide 10
receptor 5HT1 5HT2 5HT3 5HT4 5ht5 5ht6 5HT7 subtype 5HT1A, 5HT1B, 5HT1D, 5ht1E, 5HT1F 5HT2A, 5HT2B, 5HT2C 5HT3A, 5HT3B 5ht1A, 5ht1B noteworthy flagging pathway cAMP↓ IP3 particle channel cAMP cAMP? cAMP cAMP 5HT ReceptorsSlide 11
A couple words about sign transduction components…Slide 12
4 Families of Receptors Channel connected (Ionotropic) G-protein coupled (Metabotropic) Kinase-connected (enzymatic) Intracellular (quality interpretation)Slide 13
Ionotropic receptorsSlide 14
G-Protein coupled receptorsSlide 15
The Major G Proteins G s Stimulatory-Activates Ca channels, initiates adenylyl cyclase G i Inhibitory-Activates K channels, hinders adenylyl cyclase G q – Activates phospholipase C G o - Inhibits Ca channels G 12/13 – Diverse particle transporter collaborationsSlide 16
Second Messengers-Adenylyl Cyclase http://www.endocrinesurgeon.co.ukSlide 17
Second Messenger-Phospholipase C http://www.endocrinesurgeon.co.ukSlide 18
5HT 1A receptor CNSforum.comSlide 19
5HT 1A Partial Agonist systemSlide 20
5HT 1A Antagonist instrumentSlide 21
5HT 2 receptor systemSlide 22
5HT 2 Antagonist componentsSlide 23
Depression Anxiety Social fear Schizophrenia Obsessive-impulsive Panic issue Migraine Hypertension Pulmonary hypertension Eating issue Vomiting Irritable gut disorder The Swiss armed force blade of NeurotransmittersSlide 24
Serotenergic Drugs 5HT 1A Buspirone, ipsapirone treat uneasiness, sorrow (halfway agonist) 5HT 1D Sumatriptan, treat headache (incomplete agonist) 5HT 2A/2C methysergide, trazodone, risperidone, ketanserin treat headache, wretchedness, schizophrenia (foe)Slide 25
Drugs proceeded with… 5HT 3 Ondansetron treat chemotherapy-incited emesis (enemy) 5HT 4 Cisapride treat GI issue (agonist) 5HT transporter SSRIs (Fluoxetine, sertraline) treat despondency, OCD, alarm issue, social fear, post traumatic anxiety issue (inhibitor)Slide 26
Antidepressants Decreased sums and weakened capacity of 5-HT connected with hostility, discouragement and different types of standoffish conduct Antidepressants endeavor to build 5-HT levelsSlide 27
Serotonin Syndrome Toxic, conceivably lethal impacts require a mix of serotonergic specialists, for example, a SSRI with a MAOI. Side effects: elation, laziness, supported quick eye development, overcompensation of reflexes, fast muscle contraction,abnormal developments of the foot, tipsy, dazed feeling,high body temperature, shuddering , looseness of the bowels ,loss of awareness, demiseSlide 28
Treatment suspected specialists ought to be stopped OTC medications containing fixings known not serotonin levels, for example, dextromethorphan, pseudoephedrine or phenylpropanolamine, additionally ought to be suspended. Benzodiazepines for mellow to direct cases Cyproheptadine, Methysergide, and Propranolol for serious casesSlide 29
Oh man I just saw God and he was playing a mandolin and he instructed me to watch Fear and Loathing in Las Vegas while listening to The Doors self-titled collection and buddy they thoroughly go together LSD Non-specific 5HT agonist/halfway agonist Ergot subsidiary Mimics 5HT at 5HT 1A autoreceptors on raphe cell bodies, moderates terminating rate of serotonergic neurons Current speculations concentrate on glutamate discharge in thalamocortical terminals, bringing about separation between tactile hand-off and cortical yieldSlide 30
Hallucinogens and medication segregation trials Animal model thought to reflect subjective impacts Mediated by enactment of 5HT 2A receptors Acts as fractional or full agonist at 5HT 2A and 5HT 2C receptors Phenethylamine subsidiaries (psilocybin) are particular 5HT 2A/2C agonistsSlide 31
Human Studies Psilocybin and PET imaging examines design looks like cerebrum initiation in schizophrenic patients Action of psilocybin is hindered by pretreatment with 5HT 2A/2C opponentsSlide 32
Yeah rub Vaseline on my eyelids – 5-HT & MDMA causes an expanded arrival of 5-HT and squares reuptake High fondness for SERT Effects fine axons Responsible for temperature incrementsSlide 33
Receptor OverviewSlide 34
5HT 2 subtypes
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