The
adrenergic receptors (adrenoceptors) are a class of G-protein coupled
receptors, which are the targets of catecholamine’s. Adrenergic receptors
specifically bind their endogenous ligands, the catecholamine’s, epinephrine,
and norepinephrine (also called adrenaline and noradrenaline), and are
activated by these. The term adrenoblocker refers to drugs that are capable of
competing with catecholamine’s and other adrenomimetics for binding with
adrenergic receptors, thus blocking effects of sympathetic nerves caused by
either stimulation by endogenic sympathomimetic or generated by adrenergic
drugs of exogenic origin. True adrenoblockers do not affect the process of
norepinephrine (noradrenaline) synthesis in the organism.
Adrenoblocking drugs are classified as
α-adrenoblockers, β-adrenoblockers, and adrenergic neuron blockers depending on
the response brought about in the organism. α-Adrenoreceptors cause dilation of
peripheral blood vessels, and a few of them relax smooth muscles. On the other
hand, β-adrenoblockers have a minor effect on vascular tonicity. In addition,
β-adrenoblockers prevent the vasodilator effect of epinephrine. In organs such
as the heart, which are regulated mainly by β-adrenoreceptors, β-adrenoblockers
counteract the excitatory effect of norepinephrine.
In turn, α- and β-adrenoblockers are
subdivided into selective and nonselective groups. Nonselective
β-adrenoblockers exhibit affinity for both β1- and β2-adrenoreceptors.
Included in this category are propranolol, nadolol, timolol, and labetalol (a
combined α- and β-adrenoblocker). Selective β1-blockers are
acebutol, atenolol, esmolol, and metoprolol, which in therapeutic doses
predominantly binds to β1-adrenoreceptor regions. Currently, there
are no therapeutically useful selective β2- adrenoblockers, although
a number of experimental compounds with expressed β2-adrenoblocking
activity already exist.
Drugs that exhibit reversible
competitive blocking action on β-adrenoreceptive receptor system and that
counteract effects of catecholamine’s are called β-adrenoblockers. These drugs selectively reduce cardio
stimulatory, vasodilating, bronchiolitis, and metabolic (glycogen lytic and
lipolytic) action of catecholamine’s released from adrenergic nerve endings and
adrenal glands.
β1-Receptors are present in
heart tissues, and cause an increased heart rate by acting on the cardiac
pacemaker cells. Many β-blockers used for treatment of angina will mainly
affect these receptors and the β2-receptors to a lesser extent. These
are referred to as ‘cardio-selective’ β-blockers.
β2-Receptors are in the
vessels of skeletal muscle, and cause vasodilation, which allows more blood to
flow to the muscles, and reduces total peripheral resistance. These tend to
work with epinephrine (adrenaline), but not norepinephrine (noradrenaline). β2-Receptors
are also in bronchial smooth muscle, and cause bronchodilation when activated.
Some antiasthma drugs, such as the bronchodilator salbutamol work by binding to
and stimulating the β2-receptors. Nonselective β-blocking drugs, such as
propranolol, can represent a risk to people with asthma by blocking the β2-receptors,
causing bronchoconstriction.
Introduction of β-adrenoblockers into
medicine was one of the main advancements of pharmacology of the cardiovascular
system. Initially these drugs were used only in treating essential
hypertension. Currently, they are used in treating angina, arrhythmia,
migraines, myocardial infarctions, and glaucoma. Their efficacy in many
illnesses is explained by the competitive binding of β- adrenoreceptors in the
autonomic nervous system by basically any of the employed drugs of the
1-aryloxy-3-aminopropanol-2 class, which result in reduction of heart rate and
strength of cardiac beats, slowing of atrioventricular conductivity, reduction
of the level of renin in the plasma, and reduction of blood pressure. The main
effects of β-adrenoblockers are expressed at the level of the vasomotor center
in the hypothalamus, which result in a slowing of the release of sympathetic,
tonic impulses.
Practically, all of them are derivatives of
1-aryloxy-3-aminopropanol-2, the C1 position of which always possesses a
substituted or no substituted aromatic or heteroaromatic group connected by an
ether bond to a three-carbon chain. An R group at the nitrogen atom of the
propanoic region must be represented as either a tertiary butyl group (nadolol,
timolol), or an isopropyl group (the remainder of the drugs).
Levorotatory isomers of these drugs are
much more powerful adrenoblockers than dextrorotatory isomers; however, all of
these drugs are made and used as racemic mixtures. The examined drugs
reversibly bind with β-adrenergic receptive regions and competitively prevent
activation of these receptors by catecholamine’s released by the sympathetic
nervous system, or externally introduced sympathomimetic. It is important to
note that selectivity is not absolute, and it depends on the administered dose.
In large doses, selectivity is even and both subtypes of β-adrenoreceptors are
inhibited equally. In addition to blocking β-adrenoreceptors, these drugs
affect the cardiovascular system in a different manner. In addition, β-blockers
prevent the release of renin, which is a hormone produced by the kidneys which
leads to constriction of blood vessels. Drugs that block β2-receptors
generally have a calming effect and are prescribed for anxiety, migraine,
esophageal varices, and alcohol withdrawal syndrome, among others.
β-Adrenoblockers are most widely used in treating angina, hypertonic diseases,
tachycardia, and arrhythmia.
