ADRENERGIC
AGENTS
Sympathetic NS
Adrenergic NT Synthesis
- Formation of NT starts with
tyrosine entry to the pre synapse
via the Na-dependent carrier
- VMAT  vesicular monoamine
transporter
- Dopamine beta-hydroxylase
converts dopamine to NE
- Stimulation of voltage-sensitive
Ca channels causes the
stimulation of VAMPs (vesicle-
associated membrane proteins)
 fusion of vesicles  expulsion
of NE and other substances
- Some portion of NE undergo
reuptake mechanism via NE
transporter (NET)  termination
of synaptic activity of NE
NE and E are metabolized by
Monoamine oxidases (MAO) or
catechol-o-methyltransferase
(COMT); the latter acts only on
molecules with catechol nucleus
*Meta and Para position of benzene
ring are the sites of OH group
SUBSTITUTION on the BENZE
- Removal of one OH group leads
to no metabolism by COMT
- Not easily metabolized by MAO
and COMT
- Ephedrine, who has lost all
hydroxy groups, enjoys all the
advantages but may suffer less
potency compared to
catecholamines
ADRENERGIC AGONISTS
ALPHA 2 AGONISTS
Guanfacine and Guanabenz
- Relative to clonidine for HTN
 - - Same DOA with albuterol
Terbutaline
- Modification of catechol portion of
beta agonists leads to selective
beta 2 activity
- Hydroxyl groups are in meta and
another, NOT in para position
- Hydroxyl group at Beta carbon 
activity
Methyldopa - Longer DOA as it is not
- Acts as false NT metabolized by MAO or COMT
- Mimics dopa Formoterol
- Faster onset than salmeterol
- Long acting, inhalational
- Modification of catechol portion
as well as Beta-hydroxyl group
-

BETA 1 AGONIST
Dobutamine
- Has amino group substitution 
better Beta activity than alpha Ritodrine
BETA 2 AGONISTS - Used to control premature labor
and reverse fetal distress caused
Salmeterol
by excessive uterine activity
- Selectivity is due to the - Non-catecholamine
replacement of meta-hydroxyl - Substitution at alpha and beta
group of catechol ring with a carbon
methyl moiety  very long acting
(up to 12 hrs DOA)
Albuterol
- Selectivity is same with
salmeterol
- Shorter DOA = 3-6 hours
Pirbuterol

DOPAMINE AGONISTS
Dopamine
- Employed in CV shock\
- Not to be given orally as
metabolized by MAO and COMT\
OTHERS
Ephedrine
- Non catecholamine; lipophilic due
to absence of hydroxyl groups at
benzene ring
- Mixed-acting sympathomimetic
agent
- From ephedra from Ma huang
Xylometazoline and Oxymetazoline
- Direct-Alpha acting agonist
- Used as topical decongestant
- Non-selective alpha antagonist
Methamphetamine
- Differs from amphetamine via the
methyl substitution at amine
moiety of amphetamine
Pemoline
- Oxazolidine compound
- 2-amino-S-phenyl-2-oxazolin-4-
one
Tyramine
- MAOI + Tyramine  orthostatic
hypotension
Cocaine
- CNS stimulants
ADRENERGIC ANTAGONISTS
ALPHA Antagonist
Reversible Alpha Antagonist
Phentolamine
- Used to prevent and control
hypertensive episodes among
patients with pheochromocytoma
or aide in diagnosis of this
disease
- Combined with papaverine to
manage impotence
Irreversible Alpha Antagonist
Phenoxybenzamine
- Ethyleneimonium group 
intermediate form which
covalently binds to alpha receptor
(leading to irreversible activity)
Selective Alpha
Prazosin
- Quinazoline structure
- 4-amino is important for the
alpha1 receptor affinity
- Acyl group affects PK
- 1st dose phenomenon  patient
experiences marked excessive
postural hypotension and
syncope in early doses
BETA Antagonist
- Structurally similar to B agonists
- The catechol ring can be
replaced by any substituent
without losing the antagonistic
activity
- Branched bulky N-alkyl groups
are good for B-antagonistic effect
- Beta selective are those with
PARA substituent and NOT meta
substituent rings
Carvedilol
- Nonselective B blocker agent
with Alpha 1 blocking activity
- It is (+-)-1-(carbazole-4-yloxy)-3-
[[2-(o-
methoxyphenoxy)ethyl]amino]-2-
propranolol\

AGENTS DEPLETING….
Reserpine
- was used for HTN due to
inhibition of NE release thru
VMAT inhibition; used nowadays
as tranquilizer