Medicinal chemistry -l-Second year-Fourth semester - lecture V sympathomimetic agents.pptx

1. Medicinal chemistry l
Lecture V
Sympathomimetic agents
By Manjusha SK
Associate professor

2. Sympathomimetic agents
 These are the chemical agents or drugs which mimics the action of sympathetic nervous
system by reacting with the adrenergic receptors.
 These are classified as bellow :

3. SAR of Sympathomimetic agents
 Sympathomimetic drugs are considered as derivatives of ß-Phenylethylamine (Parent compound).
 Structurally, substitution is possible on—The aromatic ring,
 -Substitution on ß-carbon,
 -Substitution on α-carbon
 -Substitution on the amino group ß-phenylethylamine (Parent)

4.  2.The presence of —OH groups at 3 and 5 position with bulky substituents on amino nitrogen gives
β2 selective drug. For example, Orciprenaline
 3.Drugs having substituents other than —OH group have greater selectivity for adrenergic receptors.
For example, Salbutamol
 4.The unsubstituted or alkyl substituted adrenergic amines easily crosses the blood brain barrier and
have more CNS activity. For example, Amphetamine.
B. Substitution on the β -carbon : An —OH group on the ß-carbon decreases the central stimulant action
due to lower lipid solubility of the drug. For example, Ephedrine has less central stimulant effect.
C.Substitution on the α -carbon : Drugs having substituents on the a-carbon blocks the metabolism
caused MAO and hence these have longer duration of action. For Example Amphetamine.
D.Substitution on the amino group :
 Lesser the substitution on the amino group, higher will be selectivity for a-receptors.
 More the size of alkyl substituent„ higher will be ß-selective action
 The phenyl ring must be separated from the side chain amino group by two carbon atom.

5. A. Direct acting drugs
 A. Direct acting drugs -These agents produce a sympathetic response by interacting directly with
adrenergic receptors.
 1) Norepinephrine (NA)-
IUPAC Name-(3,4-Dihydroxyphenyl)-2-aminoethanol
 Mechanism of action k is a potent agonist at a-receptors and has little or-no effect on ß2 -
receptors but has effect on ß1-receptors. It is less potent than adrenaline.
 Uses :
1. Norepinephrine is used to reduced the absorption and to localise the effects of local anesthetics.
2. It decreases the chances of haemorrhage during an operation.
3.It is given by intravenous infusion for the treatment of hypotension.
4.It has strong vasoconstriction property.

6.  2) Epinephrine (Adrenaline)
• Mechanism of action- it is a direct acting drug. It interacts directly with a1 and ß2 receptors. It is highly
potent among all the directly acting drugs
Epinephrine inactive when given by mouth as it undergoes enzymatic degradation and
first pass metabolism in the liver. For this, prodrug of epinephrine is prepared with pivalic acid.
• Uses- It acts subcutaneously to produce vasoconstriction.
It is used in the emergency treatment of anaphylaxis and anaphylactic shock in
the cardiopulmonary disease
It relaxes bronchial muscles and is used in the treatment of asthma.
Aqueous solutions of epinephrine are used as inhalation as a spray to reduce
asthmatic spasms
It is also used in the form of spray in acute allergic rhinitis, hay fever and sinusitis.

7. • 3) Phenylephrine-
• Synthesis- It is prepared by the reaction of m-chloro-acetyl-phenol and methylamine followed by the
reduction of the intermediate formed.

8.  Mechanism Of action -It is a selective-a1 agonist and has no-action on the P-receptors. Activation
of receptors causes vasoconstriction of arterioles, iris and contraction of uterus.
 Uses -1.It is mainly used as a decongestant in rhinitis and sinusitis
2.It is used in the eye for producing mydriasis when cycloplegia is not required
3.It is used as a pressor agent in the hypotensive states like circulatory failure
or hypotension
4) Dopamine –
Mechanism of action - It interacts directly on ß-adrenergic receptors (agonist at receptors) and
indirectly on a-adrenergic receptors.
Uses – 1. Dopamine is used in patient of shock
2. It is used in severe congestive heart failure where it increases BP and urine outflow.
3. It is used intravenously in myocardial infarction and cardiac surgery.

9.  5) Salbutamol-
• Mechanism of action- It is a Strong ß2 -adrenergic agonist. It is a directly acting sympathomimetic
drug having strong action on ß2 –receptors.
• Synthesis –
•

10.  Uses- 1.orally or as an inhalation it is used for symptomatic relief of bronchospasm associated acute
or chronic asthma.
 2. It is used in the treatment of bronchitis and other obstructive pulmonary diseases.
THANK YOU