1. Sympathomimetic drugs
Dr Adedunni Olusanya

2. Classification
Direct -
Indirect
Mixed agonists

3. Indirect Amphetamine, cocaine Increased release of neurotransmitters
Decrease reuptake of NT
Decrease metabolism of NT

4. Decreased reuptake of neurotransmitters
Cocaine, tricyclic antidepressants like desipramine, ephedrine, phenoxybenzamine, guanethidine, amphetamines,
These drugs inhibit NET in the synaptic terminal
NET is an active Na coupled amine transporter located in the presynaptic neuronal membrane –uptake 1
Main mechanism for termination of action of NA- up to 90% reuptake
Has a higher affinity for NA than Adr
Inhibition - Leads to accumulation of noradrenaline in the synaptic junction – more sympathetic activity
Note decreased reuptake is not the main mechanism of action of amphetamines and guanethidine

5. Increased release of neurotransmitters
Amphetamine, tyramine, ephedrine
Because they are structurally similar to cathecholamines, they are taken up by NET.
In the cytosol they are taken up by vesicular monoamine transporter.
Thus displacing norepinephrine from the storage vesicles into the cytosol.
The displaced norepinephrine is either degraded in the cytosol by MAO or released into the synaptic junction by the process of reverse transportation via NET.
Reverse transportation involves the influx of the drugs and release of norepinephrine

6. Mechanism of action of reuptake inhibitors
Source : Rang and Dale

7. Reduced metabolism of noradrenaline
Monoamine oxidase inhibitors
Irreversible – tranylcypromine, isocarboxid
Reversible – Moclobemide , clorgylline

8. Mixed action Ephedrine and pseudoephedrine
Increase release of NT and act directly on the receptors

9. Direct sympathomimetics
They act on adrenergic receptors
Adrenergic receptors are G protein coupled receptors
They increase or reduce the production of second messenger cAMP or IP3/DAG
Sometimes they are coupled to ion channels – Calcium or potassium
Or increase prostaglandin production
Include epinephrine, norepinephrine, dopamine, dobutamine, isoproterenol, albuterol, oxymetazoline, clonidine, phenylephrine
Two major groups of adrenergic receptors – alpha and beta based on potencies of agonists

10. Properties of the receptors
Source – Rang and Dale

11. Source - Tripathi

12. Source – Rang and Dale

13. Source – rang and dale