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NEUROTRANSMITTER REGULATION
- 2. “A neurotransmitter is the body's chemical messenger. They are molecules that transmit signals from neurons to muscles, or between different neurons..”
- 10. Contents Introduction Bio synthesis Metabolism Dopamine pathway Dopominergic receptors 1 3 2 4 5 6 Dopamine Related disease Dopamine Agonist antagonist
- 12. ● Dopamine is an endogenous catecholamine that serve as both a neurotransmitter and a precursor of norepinephrine synthesis ● When given as an exogenous drug dopamine activates a variety of receptors in dose dependent manner ● It regulate Cardiac function Vascular function Endocrine function
- 14. PHYSIOLOGICAL ROLES primary regulator of prolactin secretion from the pituitary gland Pituitary increase natriuresis increase renal blood flow glomerular filtration Kidney activate B adrenergic receptors increase cardiac contractility Heart and cvc Abundace of Dopamine receptor initiate Emesis GI Tract
- 15. BIO SYNTHESIS & METABOLISM 2 Of dopamine
- 18. Storage Of dopamie • Dopamine neurotransmitters are stored in small storage packages called vesicles by the help of vesicular monoamine transporter (VMAT2)
- 20. A Hydrogenatom from the inside of the vesicle binds, inducing a conformational change in the transporter The conformational change induced by the hydrogen atom binding enables the monoamine binding to the active transport site A second hydrogen atom binds from inside the vesicle to the transporter inducing another change The monoamine is released inside the vesicle and the two hydrogen atoms are released into the cytosoland the transport process starts over again
- 21. Fusion &Release Of dopamie 2 1 FUSION Fusion of vesicle is occurred by formation of snare complex RELEASE Release of dopamine was done by exocytosis process
- 23. 5 4 2 1 3 Assembly of prefusion SNARE / SM protein complex Activation of prefusion SNARE / SM protein complex by complexin NSF- mediated SNARE- complex disassembly & vesicle recycling Fusion – pore expansion +NSF&SNAP binding Calcium triggering of fusion - pore opening Fusion Release Of dopamie
- 24. DOPAMINE D2 D3 D4 D1 D5 binding D2 D1 G PROTEIN COUPLED RECEPTOR G(S) G(I)
- 25. Reuptake Of dopamie • Reuptake of dopamine occurs mainly via dopamine transporter (DAT)
- 28. 1 3 2 4
- 29. Mesocortical Mediates cognitive and emotional behavier Mesolimbic Plays a role in emotion and reward system Tubero infundibular Regulate prolactine release Nigrostriatal Controles movement
- 32. Ventral tegmental area(VTA) Nucleus accumbens (NA) to Projection from MESOLIMBIC PATHWAY
- 41. Mesocortical Mesolimbic Tubero infundibular Nigrostriatal Schizophrenia, Psychoses (including Bipolar depression) Learning deficits Psychoses Schizophrenia, In attention-deficit Hyperactivitydisorder Hyperprolactinemia Parkinsondisease
- 47. • Levodopa Dopamine Precursors • Selegiline • Rasagiline MAO-B inhibitors • Bromocriptine (ergot) • Ropinirole • Pramipexole • Apomorphine DopamineAgonist • Tolcapone • Entacapone COMT inhibitors DOPAMINE AGONIST • Benztropine • Biperiden • Procylidine • Trihexphenidyl Anticholinergic • Carbidopa • benserazide Decarboxylase inhibitor
- 48. Levodopa 3,4-dihydroxy-L-phenylalanin L-DOPA crosses the protective BBB whereas DOPAMINE itself cannot. Thus L-DOPA is used to increase dopamine concentrations in the treatment of Parkinson's disease • PEAK PLASMA CONCENTRATION O.5 TO 2 Hours • T1/2 – 1to 3 hours • In clinical practice,levodopais almost always administered in combination with a peripherally acting inhibitor of aromatic L-amino acid decarboxylase,such as carbidopa or benserazide
- 51. ADVERSE EFFECT on/off phenomenon "wearing off" phenomenon each dose improves mobility for a period of time, Hallucinations and confusion especially in elderly patients or inpatients with pre existing cognitive dysfunction motor state may fluctuate dramatically each dose of levodopa Nausea orthostatic hypotension
- 52. WITHDRAWAL SYNDROME suddenly stopping dopamine agonist doses. It can cause a serious condition called malignant syndrome symptoms include • high fever • rigidity • loss of consciousness • kidney failure
- 54. Schizophrenia is a serious mental disorder
- 56. Mesocortical pathway Mesolimbic pathway Negative symptoms Positive symptoms
- 57. Antipsychotic Typical Mechanismof action toxicity Phenothiazines: -chlorpromazine -fluphenazine -thioridazine Thioxanthenes Thiothixene flupenthixol Blockade of D2>>5HT2A parkinson symptom hyper prolactinemia Butyrophenones Haloperidol Droperidol Blockade of D2>>5HT2A Extra pyrimidal dysfunction Clozapine is the only FDA-approved medicationfor treating schizophrenia (It highly inhibit – D4 receptorand 5HT2)
- 58. •Aripiprazole (Abilify) •Aripiprazole Lauroxil (Aristada) •Asenapine (Saphris) •Brexpiprazole (Rexulti) •Cariprazine (Vraylar) •Clozapine (Clozaril) •Iloperidone (Fanapt) •Lumateperone (Caplyta) •Lurasidone (Latuda) •Olanzapine (Zyprexa) •Olanzapine/samidorphan (Lybalvi) •Paliperidone (Invega Sustenna) •Paliperidone (Invega Trinza) •Quetiapine (Seroquel) •Risperidone (Risperdal) •Ziprasidone (Geodon)
- 59. Dopamine antagonists used to treat nausea and vomiting • Domperidone • Bromopride • Metoclopramide Dopamine antagonists used only in research • Eticlopride • Nafadotride • Raclopride
- 65. PROLACTIN Test • Males: 2 to 18 nanograms per milli litter (ng/mL) • Nonpregnant females: 2 to 29 ng/mL • Pregnant females: 10 to 209 ng/mL Prolactin Levels Are High Prolactin Levels Are Low hyperprolactinemia hypopituitarism
- 66. Irregular or no periods infertility Breast milk discharge when you’re not pregnant or nursing Tendernessin your breast Menopausal symptoms such as hot flashes and vaginal dryness Decreased sex drive Difficulty in getting an erection Breast tendernessor enlargement Breast milk production (very rare)
- 70. THANK YOU