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Neurotransmitters: Monoamines

Neurotransmitters: Monoamines. Lesson 9. CRITERIA. 1. NT found in axon terminals 2. NT released by action potentials 3. Synthesis identified 4. External application mimic normal response 5. Pharmacology same for normal and externally applied NT

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Neurotransmitters: Monoamines

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  1. Neurotransmitters: Monoamines Lesson 9

  2. CRITERIA 1. NT found in axon terminals 2. NT released by action potentials 3. Synthesis identified 4. External application mimic normal response 5. Pharmacology same for normal and externally applied NT • Mechanism of action • Actions of agonists & antagonists • Direct & indirect ~

  3. Monoamines • Amino acid precursors • single amine group • 2 groups • Catecholamines - catechol ring • Indolamine - indole ring • Affected by many of same drugs ~

  4. Catecholamines Dopamine - DA Dopaminergic Norepinephrine - NE Noradrenergic: neurons Adrenergic: drugs/receptors Epinephrine - E Adrenergic ~ Indolamine Serotonin - 5HT Serotonergic Monoamines

  5. Monoamines • Terminated by... • reuptake • MAO - monoamine oxidase • COMT - catechol-O-methyltransferase • also in liver • Reserpine  blocks storage • initially stimulates NT release • profound depletion over several days ~

  6. Indirect Monoamine Agonists • MAOI • monoamine oxidase inhibitors • Reuptake blockers • Tricyclic antidepressants • aka Non-selective reuptake inhibitors • Cocaine & Amphetamine ~

  7. Reserpine MAO MAO Monoamines A COMT

  8. Dopamine • Only in central nervous system • mostly inhibitory systems • all metabotropic • Reward • Schizophrenia • Movement • Nigrostriatal Pathway • At least 5 DA-R types: D1, D2, etc. ~

  9. Dopaminergic Drugs • Agonist • L-DOPA • Antagonists • Chlorpromazine • D1 • Haloperidol • D2 ~

  10. tyrosine hydroxylase aromatic amino acid decarboxylase DOPA DA Dopamine Synthesis Tyrosine DOPA decarboxylase • AADC (aromatic amino acid decarboxilase) is AKA DOPA decarboxilase ~

  11. Norepinephrine • Peripheral N.S. • Sympathetic neuroeffector junction • Adrenal glands • Central N.S. • Hypothalamus • Locus coeruleus • a & b groups of receptor subtypes • metabotropic ~

  12. Adrenergic Drugs • Agonists • Mescaline • Ephedrine • Clonidine • Antagonist • Yohimbine (a2) • Propranalol (b-blocker) ~

  13. tyrosine hydroxylase dopamine b hydroxylase DOPA DA NE Norepinephrine Synthesis AADC Tyrosine

  14. Serotonin • NOT a catecholamine • Peripheral • 98% in blood & smooth muscle • Central N.S. • Raphe nucleus • Hypothalamus • R subtypes: 5HT1 , 5HT2 , etc. ~

  15. Serotonergic Drugs • Agonists • SSRIs • Selective Serotonin Reuptake Inhibitors • MDMA • Ecstasy • neurotoxicity in rats & primates ~

  16. Serotonergic Drugs • Antagonists • Psilocybin • LSD • autoreceptor agonist in CNS • Buspirone • 5HT1a • Inverse agonist • ketanserin ~

  17. tryptophan hydroxylase AAADC 5-HT 5-HTP Serotonin Synthesis • 5-HTP – 5 hydroxytryptophan • 5-HT – 5 hydroxytryptamine Tryptophan

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