Sympathomimetic drugs Dr Adedunni Olusanya

Classification Direct - Indirect Mixed agonists

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

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

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

Mechanism of action of reuptake inhibitors Source : Rang and Dale

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

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

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

Properties of the receptors Source – Rang and Dale

Source - Tripathi

Source – Rang and Dale

Source – rang and dale