2005A07 Outline the main biochemical events involved in noradrenergic transmission.
Outline how these may be altered by the use of monoamine oxidase inhibitors.



·      Synthesis

·      Nerve pathway

·      Nerve terminal

·      Receptor activity

·      MAOi effect




Nerve pathway:


At the nerve terminal:

·         NAd synthesized

·         Transport into vesicles by vesicular monoamine transporter (VMAT)

·         Action potential -> ↑Ca2+ influx via L-Ca2+ -> exocytosis

·         Reuptake by norepinephrine transporter (NET)

·         Again transported into vesicles; or

·         Degradation by COMT to normetadrenaline; or

·         Degradation by COMT and MAO to vanillylmandelic acid


Receptor activation:


·   e.g. myocardium

·   Gs G protein coupled receptor (GPCR)

·   ↑activity adenylyl cyclase -> ↑cAMP -> ↑activation PKA

·   Phosphorylation of multiple targets


·   e.g. airway smooth muscle

·   Gs GPCR

·   ↑activity adenylyl cyclase -> ↑cAMP -> ↓MLCK activity


·   e.g. vascular smooth muscle

·   Gq GPCR -> ↑cleavage PIP2 -> ↑IP3 and ↑Ca2+, and ↑DAG


MAOi interference:


·   MAO-A: degrades mainly noradrenaline, serotonin, dopamine

·   MAO-B: degrades mainly serotonin, tryptamine

·   Effect: ↑monoamines at nerve terminals

MAOi drug interactions

·   Indirect acting sympathomimetics e.g. ephedrine -> ↑↑↑effect (hypertensive crisis)

·   Serotonin reuptake inhibitors: ↑↑effect (serotonin syndrome)



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