1. Sympathomimetics or Adrenergic Drugs
These are the drugs which produce effects similar to the effects produced by endogenously released adrenergic neurotransmitters.
These drugs can work at adrenergic receptors, as well as other sites of the adrenergic neuron and can affect various steps of the life cycle of the neurotransmitter.

2. Life Cycle of Norepinephrine
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3. Life Cycle of Norepinephrine
Tyrosine is transported into the noradrenergic ending or varicosity by a sodium-dependent carrier (A).
Tyrosine is converted to dopamine , and transported into the vesicle by the vesicular monoamine transporter (VMAT), which can be blocked by reserpine. The same carrier transports NE and several other amines into these granules.
Dopamine is converted to NE in the vesicle by dopamine- -hydroxylase.
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4. Life Cycle of Norepinephrine
Physiologic release of transmitter occurs when an action potential opens voltage-sensitive calcium channels and increases intracellular calcium. Fusion of vesicles with the surface membrane results in expulsion of norepinephrine, cotransmitters, and dopamine- - hydroxylase.
Release can be blocked by drugs such as guanethidine and bretylium.
After release, norepinephrine diffuses out of the cleft or is transported into the cytoplasm of the terminal by the norepinephrine transporter (NET), which can be blocked by cocaine and tricyclic antidepressants, or into postjunctional or perijunctional cells.
Regulatory receptors are present on the presynaptic terminal. SNAPs, synaptosome-associated proteins; VAMPs, vesicle-associated membrane proteins
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5. Biosynthesis of Catecholamines
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6. Metabolism of Catecholamines
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7. Autonomic and hormonal control of cardiovascular function
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8. Autonomic and hormonal control of cardiovascular function
Two feedback loops are present: the autonomic nervous system loop and the hormonal loop.
The sympathetic nervous system directly influences four major variables: peripheral vascular resistance, heart rate, force, and venous tone. It also directly modulates renin production.
The parasympathetic nervous system directly influences heart rate.
Angiotensin II stimulates aldosterone secretion, and directly increases peripheral vascular resistance and facilitates sympathetic effects
The net feedback effect of each loop is to compensate for changes in arterial blood pressure.
Thus, decreased blood pressure due to blood loss would evoke increased sympathetic outflow and renin release.
Conversely, elevated pressure due to the administration of a vasoconstrictor drug would cause reduced sympathetic outflow, reduced renin release, and increased parasympathetic (vagal) outflow.
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9. Alpha1 receptors are coupled via G proteins in the Gq family to phospholipase C leading to the formation of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG)
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10. Alpha2 receptors inhibit adenylyl cyclase and decrease cAMP
Alpha2 receptors inhibit adenylyl cyclase and decrease cAMP. Beta Receptors stimulates adenylyl cyclase and increase cAMP.
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11. Dopamine Receptors
The D1 receptor is typically associated with the stimulation of adenylyl cyclase for example, D1- receptor-induced smooth muscle relaxation is presumably due to cAMP accumulation in the smooth muscle of those vascular beds in which dopamine is a vasodilator.
D2 receptors have been found to inhibit adenylyl cyclase activity, open potassium channels, and decrease calcium influx.
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12. Adrenergic Receptors
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13. Dopamine Receptors
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14. Autonomic 3
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15. Dopamine Receptor Subtypes
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16. Autonomic 3
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17. Autonomic 3
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18. Autonomic 3
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19. Catecholamines
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20. Noncatecholamines
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21. Autonomic 3
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22. Structure Activity Relationships
Substitution on the Benzene Ring
Substitution on the Amino Group
Substitution on the Alpha Carbon
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23. Substitution on the Benzene Ring :
Maximal α and β activity is found with catecholamines, i.e. drugs having –OH groups at the 3 and 4 positions on the benzene ring.
The absence of one or the other of these groups, particularly the hydroxyl at C3, without other substitutions on the ring may dramatically reduce the potency of the drug. For example, phenylephrine is much less potent than epinephrine; indeed, α - receptor affinity is decreased about 100-fold and β activity is almost negligible .
No –OH groups on the ring means:
1-COMT is not effective, so the drug is effective orally.
2- Lipid solubility increases, so the drug has a CNS effect. For example, ephedrine and amphetamine are orally active, have a prolonged duration of action, and produce central nervous system effects not typically observed with the catecholamines.

24. Substitution on the Amino Group:
Increasing the size of alkyl substituents on the amino group tends to increase β -receptor activity. For example, methyl substitution on norepinephrine, yielding epinephrine, enhances activity at β 2 receptors.
Beta activity is further enhanced with isopropyl substitution at the amino nitrogen (isoproterenol).
Beta2-selective agonists generally require a large amino substituent group. The larger the substituent on the amino group, the lower the activity at α receptors; for example, isoproterenol is very weak at α receptors.

25. Substitution on the Alpha Carbon
Substitutions at the α carbon, block oxidation by monoamine oxidase (MAO) and prolong the action of such drugs, particularly the noncatecholamines.
Ephedrine and amphetamine are examples of - α carbon substituted compounds .