Alpha adrenergic blockers: Tolazoline, Phentolamine, Phenoxybenzamine, Prazosin, Dihydroergotamine, Methysergide.

1. UNIT-II DRUGS ACTING ON AUTONOMIC NERVOUS SYSTEM
Prepared by- Subham Kumar Vishwakarma (Asst. Prof., Department of Pharmaceutical Chemistry, UIPS, Ujjain (MP)
P a g e 1 | 3
ADRENERGIC ANTAGONIST
Adrenergic blockers are also called as antiadrenergic drugs or sympatholytics. Adrenergic blocking agents
prevent the response of effector organs to endogenous as well as exogenous adrenaline and noradrenaline.
These drugs block the actions of adrenergic drugs at alpha (α) or beta (β) adrenergic receptors.
1. Alpha Blocker
• Alpha antagonist are preventing the interaction of endogenous NTS or Sympathomimetics wit
corresponding adrenergic receptors.
• Bind specifically to alpha receptor and interfere with catecholamines and sympathomimetics action.
Role of alpha-1 and Alpha-2 antagonist
Alpha-1 Alpha-2
• Vasoconstriction
• Increased peripheral resistance
• Increased Blood pressure
• Inhibition of norepinephrine release
• Inhibition of insulin
Classification of Alpha blockers
Alpha blockers
Nonselective Selective Miscellaneous
1. Tolazoline
It is an imidazoline derivative, nonselective α-adrenergic blocker
MOA: - non-selective competitive Alpha- adrenergic receptor antagonist
Phentolamine and tolazoline are competitive α adrenergic antagonists
and block the receptor for 5-HT and it causes the release of histamine from the mast cells, which is a potent
vasodilator.
Action: Vasodilation, Pulmonary vasodilation
Irreversible
• Phenoxybenzamine
Reversible (competitive)
• Phentolamine
• Tolazoline
Alpha-1 Blocker
Prazosin
Terazosin
Doxazosin
Alpha-2 Blocker
Yohimbine
Ergot alkaloid
Dihydroergotamine
Methysergide

2. UNIT-II DRUGS ACTING ON AUTONOMIC NERVOUS SYSTEM
Prepared by- Subham Kumar Vishwakarma (Asst. Prof., Department of Pharmaceutical Chemistry, UIPS, Ujjain (MP)
P a g e 2 | 3
Uses:
• Used to increase blood flow in peripheral vasospastic condition like Raynaud's syndrome (area of
body feel numb, and cool).
• Tolazoline used in persistent pulmonary hypertension of the newborn.
• Cerebral vascular accident
• Scleroderma- skin hardening and tightening of skin.
Side effect: vertigo, Hypotension
Synthesis
2. Phentolamine
MOA: Phentolamine have both alpha 1 and alpha 2 blocking activity and produce
tachycardia. The blocking action of these agents at presynaptic alpha 2 - receptors,
contributes to their cardiac stimulatory effects by enhancing release of NE.
Uses: Phentolamine is used to prevent or control hypertensive episodes, It is an α-
adrenergic blocker used in urgent heart failure.
Side effect: Tachycardia increased gastrointestinal motility and hyperchlorhydria
3. Phenoxybenzamine
It is a Beta halo alkyl amines derivative
MOA: it is an irreversible alpha blocker and blocks both alpha-1 and alpha-
2 receptor. Phenoxybenzamine inhibits the uptake of catecholamine from
the nerve terminals.
How covalent: - Initial step involves the formation of an intermediate aziridinium ion which will form
reversible complex with the receptor. The positively charge aziridinium ion electrophile then reacts with a
nucleophilic group on the receptor resulting in the formation of covalent bond between the drug receptor which
will lead to alkylated receptor

3. UNIT-II DRUGS ACTING ON AUTONOMIC NERVOUS SYSTEM
Prepared by- Subham Kumar Vishwakarma (Asst. Prof., Department of Pharmaceutical Chemistry, UIPS, Ujjain (MP)
P a g e 3 | 3
Uses: treatment of Hypertension, urinary retention, pheochromocytoma (catecholamine-secreting tumor
derived from adrenal medulla)
Side effect: nasal congestion, broncho constriction, reflex tachycardia, congestive heart failure, cerebral
stroke, or kidney failure
4. Prazosin
It is a Quinazoline derivative, Selective Alpha-1 antagonist
MOA: It has potent alpha 1 - adrenoreceptor blocking activity
Uses: Used in treatment of hypertension and heart attack.
Side effect: nasal congestion, dizziness, tiredness, nausea, drowsiness, orthostatic hypotension
5. Dihydroergotamine
Mechanism of action: Dihydroergotamine increases the a - blocking potency and
reduces the smooth muscle stimulant activity.
Uses: used in the treatment of migraine and vasoconstriction, overdose headache.
Side effect: Vomiting blurred vision, nasal stiffness, dizziness and upset stomach
6. Methysergide
MOA: it blocks the Alpha 1 receptor, and Methysergide interacts
with serotonin (5-HT) receptors. Its therapeutic effect in
migraine prophylaxis has been associated with its antagonism at
the 5-HT receptor.
Uses: It is used to treat headache, carcinoid syndrome and
serotonin syndrome.
Side effect: Its common side effect is retroperitoneal fibrosis.