Pharmacology: Adrenergic Agents PDF

Amine group -The terminal nitrogen. Addition of a methyl group: generally increases beta selectivity As the chain length increases, so does the beta selectivity.  DOPAMINE Dopamine is the prototypical catecholamine, to which others are compared NORADRENALINE Noradrenaline has a hydroxyl group...

Amine group -The terminal nitrogen. Addition of a methyl group: generally increases beta selectivity As the chain length increases, so does the beta selectivity.  DOPAMINE Dopamine is the prototypical catecholamine, to which others are compared NORADRENALINE Noradrenaline has a hydroxyl group added to the beta carbon, increasing its alpha selectivity  ADRENALINE Adrenaline is similar to noradrenaline with an additional hydroxyl group on the beta carbon Adrenaline also has a methyl group added to the terminal amine, increasing beta selectivity  METARAMINOL Metaraminol has an additional hydroxyl group on the beta carbon Metaraminol has only one hydroxyl group on the phenol ring, so: ○ It is no longer classified as a catecholamine ○ It is not metabolised by COMT, prolonging its duration of action ○ It has reduced potency, requiring administration in higher doses Metaraminol has an additional methyl group on the alpha carbon, preventing metabolism by MAO and further prolonging its duration of action EPHEDRINE Like metaraminol, ephedrine has a hydroxyl group on the beta carbon and a methyl group on the alpha carbon Ephedrine has no hydroxyl groups on the phenol ring, further reducing its potency and increasing its elimination half-life Ephedrine has a methyl group on the amine, increasing its beta selectivity ADRENERGIC AGENT MAIN STRUCTURE  Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity. Additional SAR of Adrenergic Agonist ADRENERGIC ANTAGONIST/ BLOCKERS Clinical uses: Ø Anti-hypertensive. Ø To treat cardiac failure. Ø To control urinary output. Ø In prostatic hyperplasia. They have diverse structural features compared to catecholamines. They will block adrenergic receptors preventing catecholamines from exerting their actions. The binding is reversible in almost all cases.  SAR of Alpha 1 Blockers Alpha 2 Blockers α 2 receptors are presynaptic. Activation leads to decrease in N.A release They are used as anti-depressant ex.: YOHIMBINE