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 Mechanism of action Actions of agonists & antagonists Direct & indirect ~

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

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

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 ~

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

Monoamines Reserpine MAO A COMT

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. ~

Dopaminergic Drugs Agonist L-DOPA Antagonists Chlorpromazine Haloperidol D2 ~

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

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

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

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

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

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

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

Serotonin Synthesis 5-HT Tryptophan 5-HTP 5-HTP – 5 hydroxytryptophan hydroxylase AAADC Tryptophan 5-HTP 5-HT 5-HTP – 5 hydroxytryptophan 5-HT – 5 hydroxytryptamine