from the discussion above, clonidine and α-methyldopa act in the same way. Clonidine
also abolishes symptoms of opiate withdrawal and stimulates histamine H 2 receptors
(section 4.6.3). It seems to have an interesting psychopharmacological activity as well,
acting as an antianxiety agent that stimulates α 2 adrenoceptors and therefore decreases
NE levels.
4.3.6.2 α-Adrenergic Antagonists
Because of their peripheral vasodilator effect, these drugs are used in the treatment of
hypertension. They act beneficially in shock and frostbite by increasing peripheral cir-
culation. Some, like phenoxybenzamine, also have cholinergic effects, indicating that
these antagonists cross-react with the AChR.
Chemically, adrenergic blocking agents are a varied group, bearing little resemblance
to the adrenergic agonists, since they use accessory binding sites of the receptor.
Benzodioxanes such as piperoxan (4.49), and quinazolines like prazosin (4.50), all
carry bulky, basic side chains. Phentolamine (4.44) is a rather nonselective older drug
of imidazoline structure. There are a few “irreversible” alkylating agents such as
phenoxybenzamine (4.51) and its congeners, which carry a β-chloroethylamine side
chain capable of reacting covalently with nucleophilic -OH or -NH 2 groups. Although
these compounds are useful drugs and experimental tools, they are slowly removed
from the receptor and are therefore not truly irreversible. All of them act through IP 3 as
second messenger.
Yohimbine (4.43) is an α 2 antagonist. Yohimbine, an indole alkaloid closely related
to reserpine—an αantagonist—has been evaluated as a potential treatment for male
erectile dysfunction. Naphazoline (4.46) and other α-agonist imidazoline compounds
are nasal decongestants, used by inhalation to decrease swelling of the nasal mucosa.
Overdependence on and overuse of these drugs can lead to rebound swelling.
α-receptor blocking agents have a number of limited clinical applications. The most
specific use of an α-adrenergic antagonist is in the management of pheochromocytoma.
A pheochromocytoma is a tumor of the adrenal gland which excretes a mixture of
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