Biogenic Amines

Biogenic Amines Include catecholamine (dopamine, noradrenalin, and adrenalin), serotonin and histamine

Catecholamine Catecholamine Synthesis 𝑡𝑦𝑟𝑜𝑠𝑖𝑛𝑒 → 𝑑𝑖ℎ𝑦𝑑𝑟𝑜𝑥𝑦𝑝ℎ𝑒𝑛𝑦𝑙𝑎𝑙𝑎𝑛𝑖𝑛𝑒 (𝐿-𝐷𝑂𝑃𝐴) → 𝑑𝑜𝑝𝑎𝑚𝑖𝑛𝑒 → 𝑛𝑜𝑟𝑎𝑑𝑟𝑒𝑛𝑎𝑙𝑖𝑛𝑒 → 𝑎𝑑𝑟𝑒𝑛𝑎𝑙𝑖𝑛𝑒    

Tyrosine hydrolase adds −OH to make L-DOPA L-aromatic amino acid decarboxylase converts to dopamine Dopamine 𝛽-hydrylase creates noradrenalin Phenylethanolamine N-methyltransferase synthesises adrenaline

Catecholamine Catabolism  

Different pathways depending on if it is a neural or circulatory catecholamine Monoamine oxidase and catechol-O-methyltransferase involved in breakdown

Serotonin Synthesis and Catabolism 𝑡𝑟𝑦𝑝𝑡𝑜𝑝ℎ𝑎𝑛 → 5-ℎ𝑦𝑑𝑟𝑜𝑥𝑦𝑡𝑟𝑦𝑝𝑡𝑜𝑝ℎ𝑎𝑛 → 5-ℎ𝑦𝑑𝑟𝑜𝑥𝑦𝑡𝑟𝑦𝑝𝑡𝑎𝑚𝑖𝑛𝑒/5𝐻𝑇/𝑠𝑒𝑟𝑜𝑡𝑜𝑛𝑖𝑛 

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Synthesised from tryptophan  Tryptophan hydroxylase converts to 5hydroxytryptophan  L-aromatic amino acid decarboxylase converts to 5-hydroxytryptophan Monoamine oxidase and aldehyde dehydrogenase degrades this to 5-hydroxyindoleacetic acid

Neurotransmitter Roles   

Noradrenaline in fear, stress, memory, attention Dopamine involved in movement, addiction, vomiting, psychosis Serotonin involved in sleep, migraines, hallucinations

Drugs Affecting Noradrenalin Normal Function     

Tyrosine transported neuron → dopamine VMAT transports dopamine into vesicles where it is converted to noradrenaline Ca2+ channels cause exocytosis Binds to adrenoceptors Uptake1/NET reuptakes noradrenaline into neuron

Indirectly Acting Sympathomimetic Amines   

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Increases extracellular noradrenaline, leading to increased activation of adrenergic receptors Include amphetamine, ephedrine, tyramine Amphetamine transported into neuron by NET  Causes VMAT to release noradrenaline and amphetamine into cell  NET has reverse transport Tyramine destroyed by MAO in the gut Indications

ADHD, appetite suppressant, nasal decongestion, CNS stimulant

Adverse Effects and Toxicity Tachycardia, insomnia, psychosis, anorexia, pulmonary hypertension

Uptake1/NET Transporter Inhibitors Feature Uses Side Effects Contraindications

Despiramine Antidepressant; aims to increase noradrenaline and serotonin levels  Postural hypotension, sedation  Dry mouth, blurred vision and constipation due to interaction with muscarinic receptors Monoamine oxidase inhibitors; gives added effect

Cocaine Local anaesthesia, drug abuse  

Hypertension, excitement, convulsions Dependence

Note: Cocaine blocks NET transporters, increasing extracellular noradrenaline Monoamine Oxidase Inhibitors  

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Decreases metabolism of noradrenalin Maclobemide used to treat depression  Can cause hypotension, weight gain, insomnia, cheese effect  Contraindications include antidepressants and drugs affecting noradrenaline and dopamine When foods containing tyramine eaten, causes hypertensive crisis known as the cheese effect  Tyramine typically broken down by monoamine oxidase  Excess of tyramine causes hypertension

Drugs Affecting Serotonin Ecstasy/3,4-methylenedioxymethamphetamine   

High affinity for SERT, stopping serotonin reuptake 10x less effect for dopamine and noradrenaline transporters Used as drug of abuse, altering perception and mood elevation  Side effects include killing serotonin neurons, tachycardia, hyperthermia, panic, ADH secretion, dysphoria  Contraindications include antidepressants and serotonin-increasing drugs

Selective Serotonin Reuptake Inhibitors 

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Fluoexetine used as antidepressant to elevate serotonin levels  Side effects include nausea, insomnia, agitation, weight loss  Contraindications include other antidepressants Has less severe side effects