Medicinal Chemistry Unit II Autonomic Nervous System

JAIPUR COLLEGE OF PHARMACY, JAIPUR
B.PHARMACY, SECOND YEAR, FOURTH SEMESTER

MEDICINAL CHEMISTRY-I
Prepared by: Mrs. Nisha Dhir
UNIT-II
AUTONOMIC NERVOUS SYSTEM

The peripheral nervous system, or PNS, consists of the cranial nerves, spinal
nerves and ganglia. The peripheral nervous system subdivided into:
1. Autonomic nervous system:
a)sympathetic nervous system
b) parasympathetic nervous system
2. Somatic nervous system.
The autonomic nervous system (ANS or visceral nervous system) is the part of
the peripheral nervous system that acts as a control system functioning largely
below the level of consciousness, and controls function. It is also Responsible
for control of “involuntary” or visceral body function: like Cardiovascular,
Respiratory, Digestive, Urinary, Reproductive functions and also play the key
role in the bodies response to stress. The autonomic nervous system (ANS)
regulates the activities of cardiac muscle, smooth muscle, and glands. It is
classically divided into two subsystems:
1.SYMPATHETIC NERVOUS SYSTEM:

Allow body to function under stress
Fight or flight
Primes body for intense skeletal muscle activity
2.PARASYMPATHETIC NERVOUS SYSTEM

Maintenance functions
Rest-and-digest
Counterbalances sympathetic function
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In general nerve impulses from one division of the ANS stimulate the organ to
increase its activity (excitation), and another part inhibit the organs activity
(inhibition). Structurally, ANS includes:
a. autonomic sensory neurons (afferent)
b. integrating centers in the CNS
c. autonomic motor neurons (efferent)
ADRENERGIC NEUROTRANSMITTERS
The sympathetic system activates and prepares the body for vigorous muscular
activity, stress, and emergencies. Adrenergic drugs stimulate the adrenergic
nerves directly by mimicking the action of norepinephrine or indirectly by
stimulating the release of norepinephrine. Therapeutically, these drugs are used
to combat life-threatening disorders, which include acute attacks of bronchial
asthma, shock, cardiac arrest, and allergic reactions. In addition these drugs are
used as nasal decongestants and appetite suppressants.
In adrenergic neurons (sympathetic postganglion), the neurotransmitter released
is norepinephrine, which is also called noradrenaline. There are closely related
catecholamines (CAs), that is, adrenaline and dopamine that has minor effects
secreted by adrenal medulla and in limbic system basal ganglia, respectively.
CAs are synthesized from amino acid phenylalanine. Tyrosine hydroxylase is
the rate-limiting enzyme and its inhibition by α-methyl-p-tyrosine leads the CAs
to dissipate. Other endogenous transmitter, that is, 5-HT produced by aromatic
L-amino acid decarboxylase converts DOPA into dopamine and
methyldopamine, and then, it is converted by dopamine β-hydroxylase to α-
methyl norepinephrine. The steps involved in the synthesis of epinephrine and
norepinephrine are.
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Biosynthesis of epinephrine and norepinephrine.
Storage of CAs NA is stored in synaptic vesicles or ‘granules’ within the

adrenergic nerveTerminal. The vesicular membrane actively takes up DA from
the cytoplasm and the final step of synthesis of NA takes place inside the
vesicle which contains dopamine β- hydroxylase. NA is then stored as a
complex with ATP (in a ratio of 4 : 1) which is adsorbed on a protein
chromogranin. In the adrenal medulla the NA thus formed
forme within the
chromaffin granules diffuses out into the cytoplasm, is methylated and Adr so
formed is again taken up by a separate set of granules. The cytoplasmic pool of
CAs is kept low by the enzyme monoamine oxidase (MAO) present on the outer
surface of mitochondria.
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Release of CAs The nerve impulse coupled release of CA takes place by

exocytosis and all the vesicular contents (NA or Adr, ATP, dopamine β
hydroxylase, chromogranin) are poured out. In case of vesicles which in
addition contain peptides like enkephalin or neuropeptide Y (NPY), these
cotransmitters are simultaneously released. The release is modulated by
presynaptic receptors, of which α2 inhibitory control is dominant.
Two enzymes namely monoaminooxidase (MAO) and catechol-o-methyl
transferase(COMT) are important in the biotransformations of catecholamines.
COMT and MAO are distributed widely throughout the body, including the
brain the highest concentrations of each are found in the liver and kidney. They
differ in their cytosolic locations.
NE released intraneurally is initially deaminated by MAO to 3,4-
dihydroxyphenylglycoaldehyde (DOPGAL). The aldehyde group is reduced to
glycol by aldehyde reductase, yielding 3,4-dihydroxy-phenylethylene glycol
(DOPEG). Aldehyde dehydrogenase converts 3,4-
dihydroxyphenylglycolaldehyde to 3,4-dihydroxy-mandelic acid (DOMA). The
final commonmetabolites formed by the action of COMT are DOMA (3-
methoxy-4-hydroxy mandelic acid) isVMA (3-methoxy-4-hydroxymandelic
acid)
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Adrenergic receptor site

Adrenergic drugs
ugs exert their effects by direct action on adrenergic receptors.
There are at least two adrenergic receptor sites (alpha (α)
( ) and beta ((β)).
Norepinephrine activates primarily alpha-
alpha receptors and epinephrine activates
primarily beta receptors, although it may also activate alpha receptors.
Stimulation of alpha receptors is associated with constriction of small blood
vessels in the bronchial mucosa and relaxation of smooth muscles of the
intestinal tract. Beta receptor activation relaxes bronchial smooth muscles
mu which
cause the bronchi of the lungs to dilate. In addition beta receptor stimulatory
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effects cause an increase in the rate and force of heart contractions. As a result
increased amounts of blood leave the heart and is diverted from nonactive
organs to areas that actively participate in the body’s reaction to stress such as
skeletal muscles, brain, and liver.
Alpha receptor site
Important features of alpha adrenergic receptor sites in order of
preference are ;
1. An anionic site. The alpha-adrenergic receptor carries a negatively charged
group (phosphate). The anionic site binds with the positive ammonium group.
2. One hydrogen bonding area
3. A flat area. A non-polar area for the aromatic ring binding.
The alpha receptors fall into two groups;
(i) α1-Adrenergic receptors. They are found in the smooth muscles of iris,
arteries, arterioles and veins.
(ii) α2-Adrenergic receptors. They mediate the inhibition of adrenergic
neurotransmitter release.
Beta receptor site

Important features of this receptor site are :
1. An anionic site. It is shown that an anionic negative acid group which binds
with the positive ammonium group.
2. Two hydrogen bonding areas. It is shown as two serine with alcohol (OH)
groups form hydrogen bonding with the phenolic—OH groups of the NE.
3. A flat area. A non-polar area for the aromatic ring.
β-Adrenergic receptors are of three types. They are
(i) β1-Adrenergic receptors. They are found in the myocardium where their
stimulation increases the force and rate of myocardial contraction.
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(ii) β2-Adrenergic
Adrenergic receptors. These are found in bronchial and vascular
smooth muscles where their stimulation causes smooth muscle dilation or
relaxation.
(iii) β3-Adrenergic
Adrenergic receptors. These receptors are expressed on fat cells and
their stimulation
on causes lipolysis.
SYMPATHOMIMETIC AGENTS
Sympathomimetics are substances that mimic or modify the actions of
endogenous catecholamines of the sympathetic nervous system. Direct agonists
directly activate adrenergic receptors while indirect agonists enhance
enh the actions
of endogenous catecholamines. Sympathomimetics stimulate alpha-1
alpha adrenergic
receptors, beta-adrenergic
adrenergic receptors, and dopamine (D) receptors in various
target tissues, such as the eyes, heart, and vascular smooth muscle. The clinical
indications
ations for sympathomimetics are broad and include asthma, heart failure,
shock, and anaphylaxis.
SAR of Sympathomimetic agents
Many of the sympathomimetic drugs contain β-phenyl
phenyl ethylamine as parent
structure.
I. Phenyl ring substitution

• Substitution on the meta and para positions of the aromatic ring and on
o the
amino, α, and β positions of the ethylamine side chain influences the
mechanism of sympathomimetic action and the receptor selectivity of the drug.
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• Maximal activity is seen in β-phenyl ethylamine derivatives, containing

hydroxyl groups in the meta and para positions of the aromatic ring (catechol)
and a β-hydroxyl group of the correct stereochemical configuration on the
ethylamine portion of the molecule.
• Although the catechol moiety is an important structural feature to obtain
maximal agonistic activity at adrenergic receptors, it can be replaced with other
substituted phenyl moieties to provide selective adrenergic agonism.
• For example, replacement of the catechol function of isoproterenol with the
resorcinol structure gives the drug metaproterenol, which is a selective β2-
receptor agonist.
• In another approach, replacement of the meta hydroxyl of the catechol
structure with a hydroxymethyl group afforded Salbutamol, which shows
selectivity to the β2 receptor.
• The naturally occurring noradrenaline has 3, 4-dihydroxy benzene ring
(catechol) active at both α and β receptors. However, it has poor oral activity
because it is rapidly metabolized by COMT, the change in substitution pattern
3, 5-dihydroxy as in metaproterenol gives good oral activity. This is due to its
resistance to metabolism by COMT. It also provides selectivity for β2 receptors.
II. Substitution at nitrogen

• Amino group in phenylethylamines is important for direct agonistic activity.
• The amino group should be separated from the aromatic ring by two carbon
atoms found among the potent direct-acting agonists.
• As the bulk of the nitrogen substituent increases, α-receptor agonistic activity
decreases and β-receptor activity increases. Thus, NE that is an effective β1-
receptor agonist is also a potent α-agonist, while epinephrine is a potent agonist
at α, β1, and β2 receptors. N-tertiary butyl group enhances β2 selectivity. As the
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size increases from hydrogen in noradrenaline

norad naline to methyl in adrenaline,
isopropyl in isoproterenol, the activity of α receptor decreases and β receptor
increases.
• Primary and secondary amines are more potent direct-acting
direct acting agonists than 3°
or 4° amines.
III. Substitution on the carbon side chain

c
• Methyl or ethyl substitution on the α-carbon
carbon of the ethylamine side
sid chain
reduces direct receptor agonist activity at both α and β receptors.
• Importantly, an α-alkyl
alkyl group increases the duration of action of the
phenylethylamine agonist by making the compound resistant to metabolic
deamination by MAO.
• α-substitution
substitution also significantly affects receptor selectivity.
• Another effect of α-substitution
substitution is the introduction of a chiral centre,
centr which
has pronounced effects on the stereo-chemical
stereo requirements
ments for activity.
1.Direct acting:
a.Nor-epinephrine
Properties and uses: It is a white or brownish-white,

brownish white, crystalline powder,
slightly soluble in ethanol and soluble in water. It differs from adrenaline only
by lacking the methyl substitution
substitution on the amino ethanol. L-isomer is
fo α1 receptors and
pharmacologically active. Noradrenaline is a potent agonist for
has relative actions on β22 receptors. By acting on these receptors, the systolic
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and diastolic pressures, and usually, pulse

p pressure
re are increased. It increases
the peripheral vascular resistance. Its principle
principle use is to support blood pressure
in various acute hypotensive states, especially in myocardial shock. It is used as
a vasoconstrictor in some local anaesthetic solutions for dental
dental use.
Storage: It becomes coloured on exposure to air and light. It should be stored in
well-closed
closed airtight containers, preferably in a sealed tube under vacuum or
under an inert gas and protected from light.
b.Epinephrine
Properties and uses: Adrenaline is a catecholamine and belongs to the family

of biogenic
ogenic amines. It is a white or creamy white, sphaero-crystalline
crystalline powder. It
dissolves in solutions
ons of mineral acids, potassium hydroxide, and of sodium
hydroxide, but sparingly soluble in water, insoluble
ble in ethanol and ether. It is
used as a sympathomimetic, broncholytic, and antiasthmatic. It is used to
prevent bleeding during surgery or in case of inner organ bleeding. Because
adrenaline leads to constriction of blood
blood vessel, it is administered
administere in
combination with local anaesthetics. In this combination, anaesthetics
anaestheti have
long-lasting effect and can be administered in smaller doses. It is used in the
treatment of heart block
ock or circulatory collapse and open-angle
angle glaucoma. It is
usually the drugg of choice in acute allergic disorders and histamine reactions.
reactions
Storage: Epinephrine is light sensitive and easily oxidized on exposure to air
a
because of the catechol ring system. The development of a pink to brown colour
indicates oxidative breakdown.
eakdown. To minimize oxidation, solutions of the drug are
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stabilized by the addition of a reducing agent,

agent, such as sodium bisulphite.
Adrenaline should be stored in well-closed
well airtight containers,
tainers, which is
preferably filled with nitrogen, and protected from light.
Dose:
ose: By subcutaneous, 0.2 to 0.5 mg in 0.1% solution; intramuscularly 1 to 3
mg in a 0.2% oil suspension, repeated as required. Dosage forms: Adrenaline
injection I.P., Adrenaline eye drops/epinephrine eye drops B.P., Dilute
adrenalineinjection (1 in 10,000)/dilute
10,000)/dilute epinephrine injection (1 in 10,000) B.P.
c. Phenylephrine*
Synthesis
Properties and uses: Phenylephrine is available as hydrochloride salt.

salt It is
white, odorless, bitter taste, crystalline powder. It is soluble in water, alcohol,
and glycerol.
lycerol. It should be stored in airtight container to protect from light
ause it is decomposed by light. Phenylephrine is a selective α1-receptor
because
agonist. Oral absorption is not reliable and so it is given parenterally or topically
as eye or nasal drops.. phenylephrine predominantly acts on peripheral arterioles
results in a rise in systolic and diastolic pressures accompanied by a marked
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reflex bradycardia. Phenylephrine is used as a nasal decongestant,

mydriatricand
and as a vasopressor agent.
d. Dopamine
Properties and uses: It is a white or almost white crystalline powder, soluble

solubl in
alcohol, sparingly soluble in acetone and methylene chloride, but freely soluble
in water. It is used inn the treatment of shock. It is ineffective orally in large parts
because
ause it is a substrate for both MAO
MAO and COMT. Dopamine exerts the CVS
effects by interacting with D1-dopaminergic
D1 dopaminergic receptors especially in the renal,
mesenteric, and coronary beds. At high concentrations, dopamine acts on β1
adrenergic receptors and causes positive ionotropic effects and also dopamine
causes the release of norepinephrine.
Storage: It should be stored in well-closed
ntainers, protected from
light.
1 μg/kg/min
Dose: Acute heart failure: Adult: Initially, 1–5 g/kg/min increased gradually
gr
by up to 5–10 μg/kg/min according to the patient’s BP, cardiac output and urine
output. Up to 20–50 μg/kg/min
g/min may be required in seriously ill patients.
Dosage forms: Dopamine intravenous infusion B.P.
e. Methyldopa
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Properties and uses: Methyldopa is a white to yellowish white, odorless fine

powder, and is soluble in water.
water
well closed airtight containers, protected from
light.
f. Clonidine
Properties ans uses: Clonidine is an imidazole derivate that acts as an agonist

of alpha-22 adrenoceptors. This activity is useful for the treatment
treatme of
hypertension, severe pain.
g. Dobutamine
Properties and uses:: It is a white or almost white crystalline powder, sparingly

sparingl
soluble in water and alcohol, and soluble in methanol. It resembles dopamine
chemically, but possesses
sesses a bulky aromatic residue on the amino group despite
the absence of a β-OH
OH group. This substitution gives a compound that possesses
an asymmetric carbon atom. Thus, dobutamine exists as a pair of enantiomers
en
possessing a distinct pharmacology. The (+) enantiomer is a potent agonist at
both β1 and β2 receptors. ( enantiomer is 10 times less potent at β1 and
eceptors. The (–)
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β2 receptors. The (–)) enantiomer is a potent agonist at α11 receptors. It ac

acts by
directly interacting with α and β adrenergic receptors. Racemic dobutamine
increases the inotropic action due to α11 receptor when compared to chronotropic
actions, and the effects are mediated by β receptors. It enhances
es the automaticity
of SA node.
Storage: It should be stored
store in well-closed
closed airtight containers, protected from
light
h. Isoproterenol
Properties and uses: It is a white or almost white crystalline powder, freely

soluble
ble in water, sparingly soluble in alcohol, practically insoluble in methylene
chloride. It is a synthetic Isopropyl
Isopropyl analogue of adrenaline, acting almost
exclusively at β-receptor.
receptor. It stimulates the action of adrenaline
adrenaline and has the
advantage of being effective when given orally. It is a nonselective β agonist
and has strong β1 and β22 agonist activity.
activi Its primary use is in the treatment of
bronchial asthma. It is used as an antiarrhythmic agent and in the treatment
tr of
shock to increase heart rate.
ntainers, protected from
light.
Dose: Sublingual,
al, 10 to 15 mg 3 to 4 times/day; I.M. or S.C. 0.01 to 0.2 mg;
repeated
epeated as necessary; infusion, 1 to 2 mg per 500 ml of 5% dextrose infusion at
such a rate so as to maintain blood pressure.
Dosage forms: IsoprenalineHCl injection I.P., Isoprenaline sulphate
sulpha tablets I.P.,
Isoprenaline injection B.P.
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i. Terbutaline
Properties and uses:: It exists as a gray-white

gray white crystalline powder, odourless and
with a bitter taste, soluble in water and alcohol. The drug exhibits the properties
acting sympathomimetic agent, having predominantly β2 adrenergic
of a direct-acting
activity, and has a selective action on the β2 receptors (i.e. β22 agonist). It is used
only as a bronchodilator and in the treatment of asthma. It possesses strong β-
agonistic activity.
j. Salbutamol*
Synthesis
Properties and uses: It is a white or almost white crystalline powder, sparingly

sparing
soluble in water, but freely soluble in ethanol. It has strong β2 adrenergic
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activity. It is useful in the treatment of acute myocardial infarction, severe left

ventricular failure. It has been used to arrest premature labour and
and is effective in
ocular hypotension by topical application. It is used only as a bronchodilator
and is the drug of choice in the treatment of bronchial asthma.
light.
Dose: By oral inhalation the adult dose is 100 microgram, followed by a second
dose after 5 min, if required.
Dosage forms: Salbutamol tablets and inhaler I.P., Salbutamol pressurized
inhalation B.
k. Bitolterol
Properties and uses: Bitolterol is a prodrug

prodrug for colterol, a beta2-adrenergic
beta2
receptor agonist, bitolterol is used as its methane sulfonate salt for relief of
bronchospasm in conditions such as asthma, chronic bronchitis and emphysema.
l. Naphazoline
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Properties and uses: It is a white crystalline, odourless, and bitter compound.

compoun
The salt is soluble in water and in alcohol. They essentially exist in an ionized
form at physiological pH because
b of the very basic nature of the imidazoline
ring (pKa 9 to 10). It is a directly acting sympathomimetic
sympathomimetic drug, which is
mostly used as a local vaso-constrictor
vaso constrictor for the relief of nasal congestion
congestio due to
allergic or infarction manifestations. It is alsoo employed as an ophthalmic
solution for the relief of ocular
ocula congestion and blepharospasm.
light.
Dose: For nasal mucosa, 2 drops of 0.05% solution;
for conjunctivity, 1 to 2 drops of a 0.1% solution after every 3 to 4 hours.
m. Oxymetazoline n. Xylometazoline.
Properties and uses: It is a potent sympathomimetic agent, having marked

mar and
pronounced α-adrenergic
adrenergic pharmacologic profi le. It is found to act as a
vasoconstrictor, when applied
applie topically to mucous membranes particularly. It is
frequently employed as a local vaso-constrictor
vaso for nasal congestion
ngestion caused by
sinusitis or rhinitis.
Dose: By intranasal, 1 drop of a 0.1% solution in adult; or a spray of 0.05%
solution
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2.Indirect
Indirect acting agents:
a. Hydroxyamphetaminee
Hydroxyamphetamine possesses α-receptor

receptor stimulant activity but lacks CNS
activity. It is a powerful vasoconstrictor. Hydroxyamphetamine is used
u in the
following conditions;; Narcolepsy (sudden attack of sleep in completely
compl
inappropriate situations,Hy
Hyperkinetic syndrome in children, As an anorexiant in
the treatment of obesity.
b. Pseudoephedrinec. Propylhexedrine.
3. Agents with mixed mechanism:

a. Ephedrine b. Metaraminol
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ADRENERGIC ANTAGONISTS
An adrenergic antagonist is a drug that inhibits the function of adrenergic
receptors. There are five adrenergic receptors, which are divided into two
groups. The first group of receptors are the beta (β) adrenergic receptors. There
are β1, β2, and β3 receptors. The second group contains the alpha (α)
adrenoreceptors. There are only α1 and α2 receptors. Adrenergic receptors are
located near the heart, kidneys, lungs, and gastrointestinal tract. There are also
α-adreno receptors that are located on vascular smooth muscle. These agents
competitively antagonise the effects of the catecholamines at α and/orβ-
adrenergic receptors. Many of the side effects of these agents are postural
hypotension, sedation or depression, increased GIT motility, diarrhoea,
impaired ability to ejaculate, increased blood volume and sodium retention.
Classification :
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Alpha adrenergic blockers

The α-receptor
receptor blockers in most cases do not show selectivity of action. Thus α-
blockers have limited clinical use. α-blockers
blockers have been employed as
antihypertensives for decades. These agents enjoy wide structural variations. On
the chemical basis, various α-receptor blockers can be classified as:
1. Tolazoline
2.Phentolamine,
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Properties and uses: It is a white, odourless, bitter powder, soluble in water

and alcohol. Phentolamine is a nonselective α-adrenoreceptor
adrenoreceptor antagonist with an
immediate onset and short duration of action. In addition to α-blocking
blocking activity,
it has weak muscarnic activity in the gastrointestinal
gastrointestinal tract and weak to mild
histaminergic activity in the stomach. It is an α-adrenergic
adrenergic blocker
blocke used in
urgent heart failure. Storage: It should be stored in well-closed
well airtight
containers
iners and protected from light. Dosage forms: Phentolaminemesylate
injection I.P., Phentolamine injection B.P.
3.Phenoxybenzamine,
Properties and uses: Colourless, crystalline compound soluble in alcohol,

water, and chloroform. Irreversible antagonist with nonselective actions, a
major use of phenoxybezamine
bezamine is in the treatment of pheochromocytoma
(tumours of the adrenal medulla). It is used to treat
t peripheral
ipheral vascular diseases,
such as Raynaud’s syndrome. It has also been used in the case of shock and
an
frostbite to improve blood flow to peripheral tissues. Used in the treatment of
shock and in the treatment of pulmonary oedema. Dose: The usual dose initially
10 mg/day, increased gradually to 60 mg/day in divided doses. Dosage forms:
Phenoxybenzamine capsules B.P.
4.Prazosin
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Properties and uses: It is a white crystalline powder, soluble in water and

alcohol. A selective α
α-antagonist, prazosin, reduces peripheral vascular
resistance and lowers arterial blood pressure
pressure in both supine and erect patients.
Dizziness, headache, and palpitations can occur. Used to treat hypertension
hyp of
any degree. It has been used in decreasing cardiac overload.
overloa Storage:
Storage It should
be stored in well-closed
closed airtight containers
containers and protected from light. Dose: For
hypertension: the adult dose as hydrochloride: Initially, 500 μg twice to
thrice/day for 3–7 days, increased to 1 mg two times to three times for the next
3–7 days if tolerated and gradually increased thereafter according to the
patient’s response. Maximum dose is 20 mg/day.
5.Dihydroergotamine
6.Methysergide.
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BETA ADRENERGIC BLOCKERS:

SAR of beta blockers,
1. Propranolol*
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Synthesis:
Properties and uses: It is a white or almost white powder, soluble in water and
a
in ethanol. Currently, it is approved for hypertension associated cardiac
arrhythmia, angina pectoris, due to coronary atherosclerosis and prophylaxis of
migraine headache. It is a nonselective β-adrenergic antagonist
ntagonist and it has equal
affinity for β1 and β22 receptors.
Dose: The oral adult dose for arrhythmias is
is 10 to 30 mg 3 to 4 times/day.
Dosage forms: Prolonged-release
Prolonged release propranolol capsules B.P., Propranolol
injection B.P., Propranolol tablets B.P.
2. Metibranolol
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3.Atenolol
Properties and uses: It is a white or almost white powder, sparingly soluble in

water, but solublee in ethanol. It is a β11 selective drug with low lipid solubility.
Mainly used in the treatment
ment of essential hypertension.
Dose: The usuall dose is 50 mg/day once daily.
Dosage forms: Atenolol tablets I.P.,B.P., Atenolol injection B.P., Atenolol oral
solution B.P., Co-tenidone
tenidonetablets B.P.
4. Betaxolol
5. Bisoprolol
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6. Esmolol
7. Metoprolol
Properties and uses: It is white, odourless powder, bitter in taste, soluble in

water, alcohol, and chloroform, but insoluble in acetone and ether. It is a β1
selective antagonist used in the treatment of hypertension.
Dose: The usual initial oral dose is 100 mg given preferably once daily.
8. Labetolol
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Properties and uses: It is a white or almost white powder, soluble in water and
in ethanol. Labetalol is a medication used to treat high blood pressure and in
long term management of angina.
9.Carvedilol
Properties and uses: Carvedilol is a racemic mixture where the S(-)

enantiomer is a beta adrenoceptor blocker and the R(+) enantiomer is both a
beta and alpha-1 adrenoceptor blocker. It is currently used to treat heart failure,
left ventricular dysfunction, and hypertension.
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JAIPUR COLLEGE OF PHARMACY, JAIPUR

B.PHARMACY, SECOND YEAR, FOURTH SEMESTER

AUTONOMIC NERVOUS SYSTEM

1.SYMPATHETIC NERVOUS SYSTEM:

2.PARASYMPATHETIC NERVOUS SYSTEM

Biosynthesis of epinephrine and norepinephrine.

Storage of CAs NA is stored in synaptic vesicles or ‘granules’ within the

Release of CAs The nerve impulse coupled release of CA takes place by

Adrenergic receptor site

Beta receptor site

I. Phenyl ring substitution

• Maximal activity is seen in β-phenyl ethylamine derivatives, containing

II. Substitution at nitrogen

size increases from hydrogen in noradrenaline

III. Substitution on the carbon side chain

Properties and uses: It is a white or brownish-white,

and diastolic pressures, and usually, pulse

Properties and uses: Adrenaline is a catecholamine and belongs to the family

stabilized by the addition of a reducing agent,

Properties and uses: Phenylephrine is available as hydrochloride salt.

reflex bradycardia. Phenylephrine is used as a nasal decongestant,

Properties and uses: It is a white or almost white crystalline powder, soluble

Properties and uses: Methyldopa is a white to yellowish white, odorless fine

Properties ans uses: Clonidine is an imidazole derivate that acts as an agonist

Properties and uses:: It is a white or almost white crystalline powder, sparingly

β2 receptors. The (–)) enantiomer is a potent agonist at α11 receptors. It ac

Properties and uses: It is a white or almost white crystalline powder, freely

Properties and uses:: It exists as a gray-white

Properties and uses: It is a white or almost white crystalline powder, sparingly

activity. It is useful in the treatment of acute myocardial infarction, severe left

Properties and uses: Bitolterol is a prodrug

Properties and uses: It is a white crystalline, odourless, and bitter compound.

Properties and uses: It is a potent sympathomimetic agent, having marked

Hydroxyamphetamine possesses α-receptor

3. Agents with mixed mechanism:

Alpha adrenergic blockers

Properties and uses: It is a white, odourless, bitter powder, soluble in water

Properties and uses: Colourless, crystalline compound soluble in alcohol,

Properties and uses: It is a white crystalline powder, soluble in water and

BETA ADRENERGIC BLOCKERS:

Properties and uses: It is a white or almost white powder, sparingly soluble in

Properties and uses: It is white, odourless powder, bitter in taste, soluble in

Properties and uses: Carvedilol is a racemic mixture where the S(-)

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