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neurohumoral transmission in cns

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Ravi Kumar katukuri

This document summarizes neurohumoral transmission in the central nervous system. It discusses the various neurotransmitters and chemical mediators involved, including amino acids (glutamate, GABA, glycine), biogenic amines (dopamine, serotonin), and neuropeptides. The pathways, receptors, and functions of these neurotransmitters are described. Neurodegenerative diseases associated with deficits in these neurotransmitters are mentioned, such as Parkinson's disease, Alzheimer's, and Huntington's disease. The conclusion states that further understanding of neurotransmitter receptor subtypes may lead to improved treatments for neurological disorders.

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Neurohumoral Transmission in CNS K Ravi kumar M.Pharm 1st semester Reg no: 170604017 Department of pharmacology Manipal university
CONTENTS Introduction Neurohumoral transmission Neurotransmitters Neurodegenerative diseases Conclusion References
NEUROHUMORAL TRANSMISSION IN CNS
Anatomic organisation of the cns
Chemical mediators in the CNS Small molecules Biogenic amines Serotonin Dopamine Histamine Epinephrine Norepinephrine Amino acids Glutamate Aspartate GABA Glycine Others Acetylcholine Nitric oxide Neuromodulators Neuropeptide-y Substance-p Lipid mediators prostaglandins Growth factors Nerve growth factor Brain derived growth factor
Chemical mediators in the CNS Mediator type Examples Targets Mainfuntional role Small molecule mediators Glutamate ,GABA, Acetylcholine, Dopamine ,5HT Ligangated ion channels G-PCR Fast & slow synaptic neurotransmission Neuromodulation Neuropeptides Substance P, Neuropeptide Y Endorphins G-PCR Neuromodulation Lipid mediators Prostaglandins Endocannabinoids G-PCR Neuromodulation Neutrophins Cytokines Nerve growth factor Kinase-linked receptors Neuronal growth , survival & functional plasticity
Amino acid neurotransmitters
Metabolism and release of aminoacids
Glutamate Synthesis
Glutamate pathway MEMANTINE REMACIDINE PIRACETAM
NMDA receptor
Ionotropic glutamate receptors NMDA AMPA Kainate Agonists Glutamate Aspartate Glycine D-serin Glutamate AMPA Quisqualate Glutamate Antagonists Ap-5,CPP NBQX NBQX ACET Modulators Polyamines Cyclothiazide Piracetam Channel blockers Phencyclidine Ketamine Remacidine Location Postsynaptic Glial cells Post synaptic Glial cells Pre & post synaptic Function Synaptic plasticity Excitotoxicity Fast epsp Fast epsp Presynaptic inhibition
Metabotropic glutamate receptors Group 1 Group 1 Group 1 mGlu1 , mGlu5 mGlu2 , mGlu3 mGlu4 , mGlu6 , mGlu7 mGlu8 G-PCR Gq Gi/Go Gi/Go Agonist DHPG CHPG LY354740 L-AP4 Antagonist LY367385a S-4-CPG LY341495 CPPG Location somatodendritic Somatodendritic & Nerveterminal Nerveterminals
粒-AMINOBUTYRIC ACID
GABAergic pathway PICROTOXIN VIGABATRIN TIGABINE
GABA Receptors
Glycine Glycine particularly present in high concentrations in the grey matter of spinal cord
Properties of Inhibitory amino acid receptors GABAA GABAB Glycine Agonist Muscimol Gaboxadol Baclofen Glycine Taurine Antagonist Bicuculline Gabazine 2-hydroxy- saclofen Channel blocker Picrotoxin Strychnine Effector mechanism Ligandgated chloride channel GPCR Ligandgated chloride channel Location GABAergic neurons Pre & post synaptic Postsynaptic mainly in brain stem &spinal cord
BIOGENIC AMINES
Dopamine pathway
Dopamine pathway in Brain
DOPAMINE Receptors D1 D5 D2 D3 D4 D1 D2 Corpus striatum Hippocampus hypothalamus Substantia nigra Limbic system Midbrain Medulla oblongata Excitatory Inhibitory
5HT PATHWAY
28978077 Metoclopramide Ergotamine Methysergide Granisatron Ergotamine
Serotonin pathway in the brain
5HT receptors 5HT1 5HT2 5HT3 5HT4 GPCR GPCR GPCRIONOTROPIC Inhibitory Excitatory Ligandgated Excitatory cAMP IP3 & DAG NA+, K+ cAMP
Receptors Location Agonists Antagonists 5HT1A 5HT1B 5HT1D 5HT1F CNS Vascular smooth muscles Blood vessels Uterus, heart, GIT Buspirone Ergotamine 5-CT Trip tans Trip tans Ergotamine Methiothepin Ergotamine 5HT2A 5HT2B CNS,PNS Smooth muscles Gastric fundus LSD Methysergide Cyproheptadiene 5HT3 PNS,CNS Chloromethyl biguanide Granisetron Ondansetron 5HT4 GIT Metoclopramide
Neurodegenerative diseases Parkinsonism It is defined as a neurodegenerative disorder of extrapyramidal Nigrostriatal pathway Therapy : MAO & COMT inhibitors Alzhiemers loss of cholinergic neurons results in shrinkage of the brain and other pathological conditions Therapy : Nootropic agents Antiamyloid antibodies NMDA receptor blocker
Huntington Depletion of GABA neurons Therapy : GABA-B Agonist Ischaemic Brain Damage Decrease blood supply results in hypoxia Therapy : NMDA receptor blocker
CONCLUSION The optimistic view is that a better understanding of the particular functions of the many molecular subtypes of these targets, and the design of more subtype- specific ligands, will lead to future breakthroughs.
References 1. Bleakman, D., Lodge, D., 1998. Neuropharmacology of AMPA and kainate receptors. Neuropharmacology 37, 187204. (Review giving molecular and functional information on these receptors), 2. Barnard, E.A., 2000. The molecular architecture of GABAA receptors. In: M旦hler, H. (Ed.), Pharmacology of GABA and glycine neurotransmission. Handbook of experimental pharmacology 150. Springer-Verlag, Berlin, pp. 79100. (Authoritative review on the molecular subtypes of GABAA receptors
3. Bylund, D.B., 2007. Receptors for norepinephrine and signal transduction pathways. In: Ordway, G.A., Schwartz, M.A., Frazer, A. (Eds.), Brain norepinephrine. Cambridge University Press, London. Head, G.A., Mayorov, D.N., 2006. Imidazoline receptors, novel agents and therapeutic potential. Cardiovasc. Hematol. Agents Med. Chem. 4, 1732. (Provides an update on the elusive imidazoline receptors

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neurohumoral transmission in cns

  • 1. Neurohumoral Transmission in CNS K Ravi kumar M.Pharm 1st semester Reg no: 170604017 Department of pharmacology Manipal university
  • 2. CONTENTS Introduction Neurohumoral transmission Neurotransmitters Neurodegenerative diseases Conclusion References
  • 5. Chemical mediators in the CNS Small molecules Biogenic amines Serotonin Dopamine Histamine Epinephrine Norepinephrine Amino acids Glutamate Aspartate GABA Glycine Others Acetylcholine Nitric oxide Neuromodulators Neuropeptide-y Substance-p Lipid mediators prostaglandins Growth factors Nerve growth factor Brain derived growth factor
  • 6. Chemical mediators in the CNS Mediator type Examples Targets Mainfuntional role Small molecule mediators Glutamate ,GABA, Acetylcholine, Dopamine ,5HT Ligangated ion channels G-PCR Fast & slow synaptic neurotransmission Neuromodulation Neuropeptides Substance P, Neuropeptide Y Endorphins G-PCR Neuromodulation Lipid mediators Prostaglandins Endocannabinoids G-PCR Neuromodulation Neutrophins Cytokines Nerve growth factor Kinase-linked receptors Neuronal growth , survival & functional plasticity
  • 8. Metabolism and release of aminoacids
  • 12. Ionotropic glutamate receptors NMDA AMPA Kainate Agonists Glutamate Aspartate Glycine D-serin Glutamate AMPA Quisqualate Glutamate Antagonists Ap-5,CPP NBQX NBQX ACET Modulators Polyamines Cyclothiazide Piracetam Channel blockers Phencyclidine Ketamine Remacidine Location Postsynaptic Glial cells Post synaptic Glial cells Pre & post synaptic Function Synaptic plasticity Excitotoxicity Fast epsp Fast epsp Presynaptic inhibition
  • 13. Metabotropic glutamate receptors Group 1 Group 1 Group 1 mGlu1 , mGlu5 mGlu2 , mGlu3 mGlu4 , mGlu6 , mGlu7 mGlu8 G-PCR Gq Gi/Go Gi/Go Agonist DHPG CHPG LY354740 L-AP4 Antagonist LY367385a S-4-CPG LY341495 CPPG Location somatodendritic Somatodendritic & Nerveterminal Nerveterminals
  • 17. Glycine Glycine particularly present in high concentrations in the grey matter of spinal cord
  • 18. Properties of Inhibitory amino acid receptors GABAA GABAB Glycine Agonist Muscimol Gaboxadol Baclofen Glycine Taurine Antagonist Bicuculline Gabazine 2-hydroxy- saclofen Channel blocker Picrotoxin Strychnine Effector mechanism Ligandgated chloride channel GPCR Ligandgated chloride channel Location GABAergic neurons Pre & post synaptic Postsynaptic mainly in brain stem &spinal cord
  • 22. DOPAMINE Receptors D1 D5 D2 D3 D4 D1 D2 Corpus striatum Hippocampus hypothalamus Substantia nigra Limbic system Midbrain Medulla oblongata Excitatory Inhibitory
  • 25. Serotonin pathway in the brain
  • 26. 5HT receptors 5HT1 5HT2 5HT3 5HT4 GPCR GPCR GPCRIONOTROPIC Inhibitory Excitatory Ligandgated Excitatory cAMP IP3 & DAG NA+, K+ cAMP
  • 27. Receptors Location Agonists Antagonists 5HT1A 5HT1B 5HT1D 5HT1F CNS Vascular smooth muscles Blood vessels Uterus, heart, GIT Buspirone Ergotamine 5-CT Trip tans Trip tans Ergotamine Methiothepin Ergotamine 5HT2A 5HT2B CNS,PNS Smooth muscles Gastric fundus LSD Methysergide Cyproheptadiene 5HT3 PNS,CNS Chloromethyl biguanide Granisetron Ondansetron 5HT4 GIT Metoclopramide
  • 28. Neurodegenerative diseases Parkinsonism It is defined as a neurodegenerative disorder of extrapyramidal Nigrostriatal pathway Therapy : MAO & COMT inhibitors Alzhiemers loss of cholinergic neurons results in shrinkage of the brain and other pathological conditions Therapy : Nootropic agents Antiamyloid antibodies NMDA receptor blocker
  • 29. Huntington Depletion of GABA neurons Therapy : GABA-B Agonist Ischaemic Brain Damage Decrease blood supply results in hypoxia Therapy : NMDA receptor blocker
  • 30. CONCLUSION The optimistic view is that a better understanding of the particular functions of the many molecular subtypes of these targets, and the design of more subtype- specific ligands, will lead to future breakthroughs.
  • 31. References 1. Bleakman, D., Lodge, D., 1998. Neuropharmacology of AMPA and kainate receptors. Neuropharmacology 37, 187204. (Review giving molecular and functional information on these receptors), 2. Barnard, E.A., 2000. The molecular architecture of GABAA receptors. In: M旦hler, H. (Ed.), Pharmacology of GABA and glycine neurotransmission. Handbook of experimental pharmacology 150. Springer-Verlag, Berlin, pp. 79100. (Authoritative review on the molecular subtypes of GABAA receptors
  • 32. 3. Bylund, D.B., 2007. Receptors for norepinephrine and signal transduction pathways. In: Ordway, G.A., Schwartz, M.A., Frazer, A. (Eds.), Brain norepinephrine. Cambridge University Press, London. Head, G.A., Mayorov, D.N., 2006. Imidazoline receptors, novel agents and therapeutic potential. Cardiovasc. Hematol. Agents Med. Chem. 4, 1732. (Provides an update on the elusive imidazoline receptors