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CNS: NEUROTRANSMITTERS 1 Learning Objectives • Know Central neurotransmitters – Excitatory neurotransmitters: • Location, agonists and antagonists, molecular mechanisms – Inhibitory neurotransmitters: • Location, agonists and antagonists, molecular mechanisms • Explain Pathways in the CNS – Nor...
CNS: NEUROTRANSMITTERS 1 Learning Objectives • Know Central neurotransmitters – Excitatory neurotransmitters: • Location, agonists and antagonists, molecular mechanisms – Inhibitory neurotransmitters: • Location, agonists and antagonists, molecular mechanisms • Explain Pathways in the CNS – Nor epinephrine – Dopamine – Acetylcholine – 5-hydroxytrypatmie CENTRAL NEUROTRANSMITTERS • Aminoacids: – glutamate; GABA and glycine • Acetylcholine • Monoamines: – Dopamine, NE, 5-HT • Peptides: – neurotensin, substance P, somatostatin, NP, and TRH • Nitric oxides • Endocannabinoids Important Excitatory NTs Neurotransmitt er Recepto Agonist r Antagonist Acetylcholine M1 Muscarinic agents Pirenzepine N Nicotinic agents Bungarotoxin Glutamate NMDA NMDA. AMPA 2-amino-5phophonovaler ate 5hydroxytrypta mine 5-HT2A LSD Ketanserine 5-HT3 2-methyl-5HT Ondasetron Alpha-1 Phynylephrine Prazosin Beta-1 Dobutamine Atenolol H1 2(m-fluorophenyl)histamine phenylhistamine Mepyramine H2 Dimaprit Ranitidine Norepinephrine Histamine Important Inhibitory NTs Neurotransmitter Receptor Agonist Antagonist Opioid Mu Bendorphin Naloxone Delta Enkephalin Naloxone Kappa Dynorphin Naloxone 5-HT 5-HT1A LSD Metergoline, spiperone Glycine Taurine Beta-alanine Strychnine NE Alpha-2 Clonidine Yohimbine Beta-2 Salbutamol Butoxamine Acetylcholine M2 Bethanechol Atropine Dopamine D1 - Phenothiazine D2 Bromocriptine Phenothiazine GABA a Muscimol Picrotoxin GABA b Baclofen 2-OH saclofen GABA Amino acid transmitters and its metabolism • Amino acid transmitters – Glutamate – GABA – Glycine • Metabolism of amino acid NTs in the brain Transport of glutamate and glutamine by neurons and astrocytes Structures of agonists acting on glutamate, GABA and glycine receptors KETAMINE Noradrenaline pathways in the brain • • • • • • • • • • • • Am-amygdaloid nucleus C-cerebellum Hip-hippocampus Hyp-hypothalamus LC-locus coeruleus MFB-medial forebrain bundle NTS-nucleus tractus solitarius RF-reticular formation Sep-septum SN-substantia nigra Str-corpus striatum Th-thalamus Dopamine pathways in the brain • P-pituitary gland – innervated with dopaminergic fibres from the hypothalamus • Ac-nucleus accumbens Am-amygdaloid nucleus C-cerebellum Hip-hippocampus Hyp-hypothalamus MFB-medial forebrain bundle NTS-nucleus tractus solitarius RF-reticular formation Sep-septum SN-substantia nigra Str-corpus striatum Th-thalamus 5-HT pathways in the brain Am-amygdaloid nucleus C-cerebellum Hip-hippocampus Hyp-hypothalamus Sep-septum SN-substantia nigra Str-corpus striatum Th-thalamus Acetylcholine pathways in the brain Am-amygdaloid nucleus C-cerebellum Hip-hippocampus Hyp-hypothalamus Sep-septum SN-substantia nigra Str-corpus striatum Th-thalamus REFERENCE NTs in the central nervous system_1 NT Anatomy Recepto r and Agonist s Antagonists Mechanisms Ach Cell bodies at all levels; long and short axons M1 Pirenzepine , Atropine ↓K conductance; ↑ IP3, DAG E M2 Atropine ↑K conductance; ↓ cAMP I Nicotini c: nicotine αbungarotoxi n ↑ cation conductance E D1 Phenothiazi nes ↑ cAMP D2: Bromoc Phenothiazi nes, Presynaptic:↓C a2 Motoneuron-Renshaw cell synapse Dopami Cell bodies at all ne levels; short, medium, and long Natur e I (?) I NTs in the central nervous system_2 NT Anatomy Receptor and Agonists Antagonist s GABA Supraspin al and spinal interneur ons GABA A: muscimol Bicuculline, ↑ Cl conductance Picrotoxin I GABA B: Baclofen 2-OH saclofen Presynaptic: ↓ Ca2 Postsynaptic: ↑ K+ I NMDA Dizocilpine ↑ cation conductance, particularly Ca2 E AM PA: AMPA CNQX ↑ cation conductance E MCPG Presynaptic: ↓ Ca2 I ↓ K+ conductance; ↑ lP3, DAG E Glutamat e Relay neurons at all levels Mechanisms Nat ure Kainate Metabotrop ic: ACPD NT NTs in the central nervous system_3 Anatomy Receptor Antagonist Mechanisms and Agonists s Nat ure Glycin e Spinal Taurine, βinterneurons alanine and some brain stem interneurons Strychnine ↑ Cl conductance I 5-HT Cell bodies in mid brain and pons 5-HT1A: LSD Metergolin e, spiperone ↑ K+ conductance ↓ cAMP I 5-HT2A:LSD Ketanserin ↓ K+ conductance; ↑ lP3, DAG E 5-HT3: 2methyl-5HT Ondansetr on ↑ cation conductance E ↓ K+ conductance E 5-HT4 NT NE NTs in the central nervous system_4 Anatomy Cell bodies in pons and brain stem Receptor and Agonists Antagoni sts Mechanisms Na tur e α1phenyleph rine Prazosin ↓ K+ conductance; ↑ lP3, DAG E α2clonidine Yohimbin e Presynaptic: ↓ Ca2 I I ↑ K conductance, ↓ cAMP β1isoprotere nol, dobutamin e Atenolol, practolol ↓ K+ conductance ↑ cAMP E β2- Butoxami ↑ cAMP I NT Histam ine NTs in the central nervous system_5 Anatomy Receptor Antagonis Mechanisms and Agonists Cells in ventral posterior hypothala mus ts H1: 2(mMepyrami fluorophe ne nyl)histamine H2: dimaprit ↓K conductance, ↑ IP3, DAG E Ranitidine ↓ K conductance, ↑ cAMP E H3: R-αThiopera methylmide histamine Opioid Cell bodies Mu: at all bendorph levels in Natur e Naloxone Delta: Naloxone enkephali n IA Presynaptic:↓ Ca2 conductance I Postsynaptic: ↑ K conductance, ↓ cAMP I NT NTs in the central nervous system_6 Anatom Receptor Antagonist Mechanism Tachykinins y and Agonists s Primary sensory neurons NK1: Substance P methylester, aprepitant s Na tur e Aprepitant ↓ K E conductanc e, ↑ IP3, DAG NK2 NK3 Endo cannabinoi ds Widely CB1: Rimonaba distribut Anandamide, nt ed 2arachidonygl ycerol Presyantpt I ic: ↓ Ca2 conductanc e, ↓ cAMP Notes