Adrenergic system

• In fight Or flight Concentration increases leading to:• Increase heart rate and cardiac output.• Increase ATP formation.• Stimulate the conversion of liver glycogen into blood

glucose.• Smooth muscles of the bronchioles relax in the lung

Adrenergic system

presynaptic postsynaptic

Termination of adrenergic activity

• 1- Uptake ( the most effective)• 2- metabolism ( COMT & MAO)• Diffusion through out tissues.

Adrenergic drugs

• Directly acting• Indirectly acting • Mixed

indirect

• Inhibits neurotransmitter reuptake.• Increase transmitter release.• Inhibit MAO.• Direct alpha agonist.• Amphetamine. & ephedrine• SAR ( no phenolic OH, benzylic OH not

necessary, steriochemisty not important as direct).

SAR (Directly acting)1- phenethylamine ( parent structure).2-Phenolic hydroxyl grps preferebly 3 & 4, at least meta hydroxy.

3-benzylic OH steriochemistry is R.4- N-substituationcarry one H9 Primary and

secondary).5- Alpha carbon could carry smal gp as CH3 and

Ethyl.

Beta 2 Agonist• 1- 3ry butyl group at N (amine)• Resorcinol Structure• terbutaline

• Manibulate the 3- OH– Sulfonamide( soterenol).– Hydroxymethyl( salbutamol).– Methylamino– Fused ring.

Ethyl group at alpha Carbon.Insertion of OCH2 betn aryl and hydroxy Eg prenalterol

B-Adrenergic agonists

Synthetic strategies

B-antagonist

• SAR• Ethanol amines ( isoproternol modifications) • a. Replacement of the ring hydroxy ( dichloro analogue)• B. Replacement with phenyl ( pronethalol).• C. N substituation. Disubstitution no activity. • Length of substituent can be increased up to 4 Cs.• N substituent should be bulky ( general)

• Aryloxypropanolamine ( propranolol)• Hydroxy group in the side chain is necessary.

Synthesis of propranolol

Alpha adrenergic

• Alpha 1-agonist• Eg phenylephrine, act as vasoconstrictor

( nasal decon & hypotension).

• Alpha 1- antagonist• Eg prazosin 7 piperpxan.• Treat hypertension.

Alpha adrenergic

• Alpha 2 agonist• Clonidine, naphazoline

• Antagonist• Eg Yohimbine.

Irriversible blocker