04 - 4. Noradrenaline

4. Noradrenaline

© SPMM Course 4. Noradrenaline

•tyrosine l-dopa dopamine  norepinephrine  epinephrine Source Source •tyrosine hydroxylase Rate limiting step Rate limiting step •dopamine-b-hydroxylase modulates norepinephrine production; phenylethanolamine-N-methyltransferase modulates conversion of NEN to epinephrine. Synthetic enzymes Synthetic enzymes •Monoamine oxidase (MAO – A especially) & Catechol-o-methyl transferase (COMT). Breakdown enzymes Breakdown enzymes •3-methoxy-4-hydroxyphenylglycol (MHPG) & VMA – vanillyl mandelic acid. •MHPG is the major metabolite in CNS while VMA is major metabolite from peripheral nervous system/endocrine system. Breakdown product Breakdown product •noradrenaline reuptake channel (tricyclics, reboxetine inhibit this) Reuptake Reuptake •arousal, anxiety, mood regulation, autonomic mediation Function Function •2 major types; α and β. •α divided into a1 and a2 •α1 receptors phospholipase C coupled; mostly postsynaptic •α2 receptors Gi coupled ; mostly presynaptic autoreceptors •β-receptors Gs coupled; predominate locus ceruleus – may regulate a •β1-receptors – high affinity to norepinephrine and β2-receptors – high affinity to epinephrine. Receptors Receptors •Levels low in depression and abnormal in panic/anxiety disorders. Disorders Disorders