It gives information about drugs acting against adrenergic nervous system. Any queries or suggestions are hearty welcomed.

1. SYMPATHOLYTIC AGENTS
BY
RAAJITA.I

2. ❖ Introduction
❖ Adrenergic receptors
❖ Adrenergic
neurotransmitters
❖ Classification of drugs
❖ SAR of β- blockers
❖ Synthesis of Tolazoline &
Propranolol
Contents
discussed

3. Introduction
● Sympatholytics are also known as anti-adrenergics or adrenolytics or
adrenergic blockers.
● These agents prevent the response of effector organs to endogenous
and exogenous adrenaline & noradrenaline by blocking actions at ∝ &
β receptors.
● All these agents are competitive agonists in their interactions with ∝ &
β receptors. One exception is phenoxybenzamine (irreversible
antagonist).

4. Nervous system

5. ● Autonomic nervous system involves Sympathetic & Parasympathetic
systems.
● Sympathetic NS is responsible for Fight / Flight responses while
Parasympathetic NS shows Maintenance of response.
● Sympathetic system involves neurotransmitters which are chemically
Catecholamines and named as follows:
Dopamine Shows pleasure and causes addiction
Epinephrine Increases heart rate
Norepinephrine Causes vasoconstriction

6. Adrenergic receptors (GPCR - type)
𝛼 - receptors
● 𝛼1- receptors: present at
postsynaptic receptor sites to
show increased excitatory action
● 𝛼2 - receptors: present at pre &
postsynaptic receptor sites and
shows inhibitory action
Ꞵ - receptors
● 𝛃1- receptors: present at cardiac
tissue and shows excitatory action (↑
blood pressure)
● 𝛃2- receptors: present at smooth
muscles & gland cells to show
inhibitory action (relaxation)
● 𝛃3- receptors: present in adipose
tissue and urinary bladder that leads
to lipolysis & relaxation respectively

7. Adrenergic neurotransmitters
Dopamine Adrenaline Noradrenaline

8. Synthesis, release and fate of neurotransmitters:
● The dopamine is synthesised from phenylamine in the presence of DOPA
decarboxylase which gives noradrenaline and adrenaline in the presence of
β- hydroxylase and N- methyl transference respectively.
● It is stored in chromaffin granules along with ATP & chromogranin-A that
diffuses into cytosol.
● Entry of calcium into presynaptic nerve terminal that undergoes
depolarisation and causes exocytosis of noradrenaline and adrenaline into
synaptic cleft.
● When the neurotransmitter binds to ∝1 receptor increase in activity is
observed and vice versa in case of ∝2 receptor (known as feedback
mechanism)

9. ● The adrenergic neurotransmitters are metabolised in the presence of
Monoamine Oxidase (MAO)
Catechol O-Methyltransferase (COMT)
● MAO gives end product named as ‘3,4- dihydroxy phenyl
glycolaldehyde’.
● COMT gives end product named as ‘4- hydroxy-3- methyl phenyl
glycolaldehyde’.

10. Classification of adrenergic blockers
● The adrenergic blocking agents are classified into two types as follows:
1. ∝ - adrenergic blockers
2. β - adrenergic blockers
● These agents act by blocking respective receptors competetively and
inhibits the action of adrenergic neurotransmitters.

11. 1. ∝ - adrenergic blockers:
a) Non -selective ∝- adrenergic blockers:Tolazoline, Phentolamine
➔ These agents stimulates gastrointestinal smooth muscles, increases
gastric secretions through histamine release, thus their clinical uses are
limited.
➔ Blockade of ∝2- receptors at presynaptic nerve terminal prouduce
cardiac stimulatory action due to increase in noradrenaline release.

12. ◆ Tolazoline is used to treat persistant pulmonary hypertension in new borns.
◆ Phentolamine prevents hypertension episodes & pheochromocytoma*.
Pheochromocytoma* is
a hormone-secreting
tumor that occurs in
adrenal gland & leads to
increase in blood
pressure.

13. ➔ Phenoxybenzamine is a β- haloalkyl amine which binds to both the ∝-
receptors
irreversibly due to β- haloalkyl group(aids in formation of covalent bond with
receptor)
➔ It is used for the preventive management of patients with pheochromocytoma.

14. c) Selective ∝1 and ∝2 adrenergic receptor blockers:
➔ Prazosin is a piperazin member which is substituted by furan-2-ylcarbonyl
group and a 4-amino-6,7-dimethoxy quinazolin-2-yl group at positions 1 & 4
respectively.
◆ It is used ti treat hypertension in combination or alone.
◆ The amine group on quinazoline ring is responsible for ∝1 receptor affinity.
➔ Dihydro ergotamine is used to treat migraines and also for medication
overusage headache or headache from withdrawl of analgesics.
◆ It is a ergot alkaloid which is marketed in the name of D.H.E.45 nasal spray.

15. ➔ Methyl sergide is used in prophylaxis and migraine treatment along eith cluster
headaches.
◆ It has been commercialized in the name of Deseril and Sansert.
◆ It was withdrawn from US & Canada market due to its adverse effects.

16. 2. β - adrenergic blockers:
a) Non - selective β - blockers: Propranolol, Metiprolol, Labetolol, Carvediol.
➔ Propranolol is a β blocker with membrane stabilizing activity, also refered to as
local anesthetic effect.
◆ Currently used for hypertension, cardiac arrhythmias, angina pectoris,
post myocardial infractions, phochromocytoma and in migraine
prophylaxis.
◆ It acts by blocking β receptors of the heart and reduces the force of
contraction & cardiac output.
◆ It is contraindicated in asthma patients because of its non- selectivity.

17. ➔ Metiprolol is used to treat open angle glaucoma as it lowers the intraocular
pressure with virtually no effect on pupil size.

18. b) selective β1- adrenergic blockers: Atenolol, Metaprolol, Betaxolol, Esmolol.
➔ Atenolol is used to traet hypertension and glaucoma.
◆ It is also approved for the tratment of angine pectoris.
➔ Metaprolol is used for angina pectoris and also to traet hypertension.

19. ➔ Betaxolol used in th treatment of glaucoma.
➔ Esmolol is a short acting antihypertensive used for short term control of heart
rate.
◆ It is also used to treat cardiac arrhythmias.
➔ Bisoprolol is an antihypertensive agent.