Sympathomimetics Classification and SAR.ppt

Classification and SAR of sympathomimetic drugs

1. SYMPATHOMIMETICS / ADRENERGIC
DRUGS: CLASSIFICATIONANDSAR

2. ACCORDINGTOCHEMICALNATURE
Catecholamines: possess catechol nucleus
e.g. Adrenaline, Nor-Adr, Dopamine
Non-catecholamines: no catechol nucleus
e.g. Ephedrine, Metaraminol

3. ACCORDINGTOMODEOFACTION
Direct acting: Act directly on receptors.
E.g. Adr, Nor-Adr, Isoprenaline and Salbutamol
Indirect acting: Act on adrenergic neurons to release Nor-Adr.
E.g. Tyramine, Amphetamine.
Mixed acting: Can act in both ways. E.g. Ephedrine

4. ACCORDINGTORECEPTORSELECTIVITY
α1 selective: Phenyl ephrine
α2selective: Clonidine
Both α1 and α2 selective: Adr and Nor Adr

5. β1selective: Dobutamine
β2 selective: Salbutamol
Both β1 and β2 selective: Adr, Nor Adr, Isoproterenol

6. ACCORDINGTOTHERAPEUTICEFFECT
Vasoconstrictor: Adr, Nor-Adr, Ephedrine, Phenylephrine
Bronchodilator: Salbutamol, Terbutaline, Isoprenaline
Cardiac stimulant: Adr, Isoprenaline
CNS stimulant: Amphetamine, Methamphetamine
Nasal decongestant: Ephedrine, Naphazoline, Oxymetazoline,
Xylometazoline
Anorectics-Fenfluramine, Sibutramine(But banned due to serious side
effects like heart attack)

7. ADRENORECEPTORS
G-protein coupled receptor.
Located throughout the body on neuronal and non-
neuronal tissues.
2 types-αand βreceptors
αreceptor is further of 2 subtypes –α1 and α2
βreceptor is further of 3 subtypes –β1, β2 and β3

8. ADRENORECEPTOR , DISTRIBUTION, ACTION
ReceptorLocationAction Use Agonist Antagonis
t
α1
Blood
vessels
Contraction Hypotension,
Shock Phenylephrin
e
Prazosin
(Antihypert
ensive)
Eye Dilation Mydriatics
Mucus
memb
VasoconstrictionNasal
decongestant
Prostate
gland
Contraction
α2 CNS Decrease
neurotransmitter
release
Antihypertens
ive Clonidine
(Antihyperten
sive)
Yohimbine
Pancreatic
cells
Decrease insulin
release

9. ReceptorLocationAction Use Agonist Antagonist
β1
Heart
muscle
Muscle contractionIncrease
heart rate
and forceDobutamineMetoprolol
(Antihyperte
nsive)
Kidney Increase renin
secretion
Increase
BP
β2 Smooth
muscle
(Bronchus)
Relaxation
(Bronchodialation)
Asthma
and COPD
SalbutamolButoxamine
β3 Adipose
tissue
Lipolysis BRL 37344

10. SAR OFSYMPATHOMIMETIC DRUGS
Parentstructureofmostofadrenergicdrugsisβ-phenylethylamine.
Modificationsofβ-phenylethylamineinfluencenotonlythemechanism
ofaction,thereceptorselectivity,butalsotheirabsorption,oral
activity,metabolism,andthusdurationofaction(DOA).
Forthedirect-actingsympathomimeticamines,maximalactivityis
seeninβ-phenylethylaminederivativescontaining
(a)catechol
(b)OHgroupontheethylamineportionofthemolecule.

11. Highadrenergicactivityoccurswhentwocarbonatomsseparatethe
aromaticringfromtheaminogroup.
Primaryandsecondaryamineshavegoodadrenergicactivity,whereas
tertiaryaminesandquaternaryammoniumsaltsdonot.
Thenatureoftheaminosubstituentalsoaffectsthereceptorselectivityof
thecompound.Asthesizeofthenitrogensubstituentincreases,α-receptor
agonistactivitygenerallydecreasesandβ-receptoragonistactivity
increases.
Substitutionbysmallalkylgroupatα-carbon(e.g.,CH3-orC2H5-)slows
metabolismbyMAO.So,additionofsmallalkylgroupincreasesthe
resistancetometabolismandlipophilicity,sosuchcompoundsoftenexhibit
enhancedoraleffectivenessandgreaterCNSactivitythanothercompounds
thatdonotcontainanα-alkylgroup.
Substitutionatβ-CbyOHgreatlyenhancesagonistactivityatbothα-and
β-receptors.

12. Compoundswith3,4-dihydroxygroupinphenylnucleusactasdirectacting
drugswhereaswithoutcatecholnucleusactasindirectactingdrugs.
CompoundswithoutoneorbothphenolicOHsubstituentsarenot
metabolizedbyCOMT,andtheyareorallyactiveandhavelongerduration
ofaction.