This document discusses noradrenergic transmission and classification of adrenoceptor agonists and antagonists. It describes the effects of agonists on alpha and beta receptors, including their pharmacological actions on the cardiovascular, respiratory, and other body systems. It also summarizes the clinical uses of adrenoceptor agonists and antagonists for conditions like hypertension, heart disease, glaucoma, and others. Drugs that affect neurotransmitter release and uptake like reserpine, guanethidine, and cocaine are also briefly discussed.

1. S A Z A N J . A L I
M S . C S T U D E N T / M E D I C I N A L C H E M I S T R Y D E P A R T M E N T
NORADRENERGIC
TRANSMISSION

2. NORADRENERGIC TRANSMISSION
-receptors
1 (causes
vasoconstriction,
mydriasis)
2 (inhibit insulin
&renin release)
-receptors
1 (increases all cardiac properties
,renin & insulin release & lipolysis)
2 (vasodilation, relax all non vascular
smooth muscles, increase liver & muscle
glycogenolysis)
3 (inhibit production of leptin)
Leptin is a protein
produced and
secreted by adipose
tissue & has a role in
regulation of eating

3. CLASSIFICATION OF ADRENOCEPTOR
AGONISTS
.Epinephrine
.Norepinephrine
.Isoprotrenol
.Dopamine
catecholamines
.Phenylephrine
.Ephedrine
.Amphetamine
Non
catecholamines
• inactivation by COMT,
MAO enzymes inactivate
within other tissues as in
liver & gut wall.
• Short duration of action.
• Poor penetration into the
C.N.S.
• Lacking hydroxyl group.
• Long half life.
• Given orally.
• Penetrate better to C.N.S.

4. CLASSIFICATION ACCORDING
MECHANISM OF ACTION
1//Direct -acting agonists
Ex//Epinephrine, Norepinephrine, Isoproterenol,
Phenylephrine
2//Indirect-acting agonists
Taken up into the presynaptic neuron & cause the release of
norepinephrine
e.g. Amphetamine
3// mixed-acting agonists
Ex//Ephedrine

5. PHARMACOLOGICAL ACTION OF
SYMPATHOMIMETIC DRUGS
 CVS effect
1 in the heart: positive inotropic and chronotropic
,increase cardiac out put and increase oxygen demands
on myocardium.
2 in smooth muscle : dilate smooth muscle of blood
vessels.
1 in the vascular smooth muscle : Vaso constriction of
blood vessels in the skin & mucous membranes leading to
 in mean blood pressure

6.  Effect on Eye
1 : mydriasis.
In open-angle glaucoma decrease production of aqueous
humor by vasoconstriction of the ciliary body blood vessels.
 Effects on respiratory tract
2 : potent bronchodilator
1: causes vasoconstriction of blood vessels of the upper respiratory tract
mucosa causes decongestion.
GIT :
Relaxation of GIT S.M through 2 & 2
PHARMACOLOGICAL ACTION
CONT…

7.  Metabolic effect
2:
• glycogenolysis (hyperglycemia).
• Lipolysis .
2:
• Decrease insulin release.
3 :
• Inhibit the production of leptin by adipose tissue
CONT….

8. Other effects
• 2 : Delay premature laboure through
relaxing uterine smooth muscles.
o α1 : stimulate smooth muscle proliferation in
various tissues. E.g.: prostate.
o 1 : stimulate renin secretion.
o α2 : inhibit renin secretion.

9. Clinical uses of adrenoceptore agonists
• Cardiovascular system :
-cardiac arrest: Adrenalin
-cardiogenic shock: Dobutamine (beta1-
agonist)
• Anaphylaxis : Adrenalin
• Respiratory system:
-asthma(selective 2 –receptor agonists)
salbutamol, terbutaline ,salmetrol, formoterol
- nasal decongestion: drops containing
xylometazolin ,ephedrin for short term use.
• Miscellaneous indication :
-adrenalin prolong the duration of local
anesthetics.
• Premature labour : salbutamol
- 2 agonists : (clonidine) to lower blood
pressure and to reduce frequency of migraine
attacks.

10. ALPHA-RECEPTOR ANTAGONISTS
• Phenoxybenzamin and phentolamine
Non selective
• Prazosin , terazosin , doxazosin
1 - selective antagonists:
• Yohimbine , idazoxan
2 –selective antagonists

11. -adrenoceptor antagonists
• phenoxybenzamine : Blocks both 1 and 2
irreversibly . Blocks the action of histamine ,Ach
& 5HT. Long-acting (24hrs).
• Pentolamine : Produces a competitive blocking
of 1 & 2 receptors.-short acting (few hrs). Both
drugs cause:
• 1) Postural hypotension.
• 2) Reflex tachycardia
• Increase in C.O. & H.R. ( reflex response to the
fall in B.P, mediated through - adrenoceptors,
also due to block 2 in heart ).
• Prazosin (short half-life) ,doxazosin & terazosin
(long half life ) allowing once-daily dosing.
• 1–antagonists cause vasodilatation & fall in
arterial pressure, but less tachycardia than with
non-selective  blockers.
• tamsulosin : is a selective 1A antagonist
,useful in patients with urinary retention due to
prostate hypertrophy.
• Yohimbin: selective 2 antagonist , its not used
clinically.
Phenoxybenzamine
used in case
pheochromocytoma
in preparation for
surgery.

12. BETA-ADRENOCEPTOR
ANTAGONISTS
Non selective
•Propranolol , l, Labetalol ,Sotalol .
•Carvedilo)also act as alpha blocker)
Selective 1
•Atenolol , Bisoprolol ,Esmolol ,
Metoprolol

14. PHARMACOLOGICAL ACTION
• CVS :
Negative inotropic and chronotropic effects.
Lowering blood pressure.
• Respiratory tract:
bronchoconstriction
• Eye :
Reduce intraocular pressure (In open-angle glaucoma) due to
decresing aqueous humor production from the ciliary
epithelium e.g. timolol.
• Metabolic and effects on endocrine secretion :
• Inhibit lipolysis , glycogenolysis & decrease glucagon
secretion.
• Increased Na+ retention.

15. • Labetalol a competitive ,antagonsits is
effective in hypertension. -blockers are less
effective in blacks & the elderly.
• IHD
• Reduce the frequency of anginal episodes.
Improve exercise tolerance. Decrease
cardiac work & oxyge demand. Reduce
heart rate.
• In supraventricular & ventricular arrhythmias.
Sotalol has potassium channel blockade in
addition to its –blockade .
• Chronic heart failure with metoprolol, &
carvedilol ( myocardial remodeling & risk of
sudden death).
• Decrease intra ocular presure through
decreasing the production of aqueous
humor. Timolol & related -antagonists are
suitable for local use in the eye .
• Blockade of catecholamine-induced
vasodilation propranolol as a prophylactic
agent used for migraine.
• Hypertension
• Ischemic heart
disease
• Arrhythmia
• Glaucoma
• Hyperthyroidism
• Neurological
disease
C L I N I C A L
U S E S

16. CHOICE OF -ADRENOCEPTOR
ANTAGONISTS
• Pindolol & acebutolol (Intrinsic sympathominetic activity )
• They are effective in hypertensive patients with moderate
bradycardia.
• Carbohydrate metabolism is less affected , making them
valuable in treatment of diabetics
• Labetalol & carvedilol (,-blocker)
• Are reversible -blockers with concurrent 1-blockers that
cause peripheral vasodilatation decrease B.P, effective for
treatment of hypertension in patients with increased
peripheral vascular resistance.

17. DRUGS AFFECTING NEUROTRANSMITTER
RELEASE/UPTAKE
Reserpine:
• Depletion of norepinephrine levels in the adrenergic
neurons. Hypertensive patients show a gradual
decline in B.P & H-R. Reserpine has a slow onset &
long duration of action.
Guanethidine:Blocks the release of stored
norepinephrine. This lead to gradual drop in B.P &
H-R. Used in the treatment of hypertension.
Guanethidine causes orthostatic hypotension &
male sexual dysfunction.

18. Cocaine:
Has a local anaesthetic action by blocking sodium
channels across the cell membrane of the
adrenergic neuron. Norepinephrine accumulates in
the synaptic space resulting in the potentiation of the
actions of Sympathomimetics. Cocaine is a C.N.S
stimulant drug.