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75
Drugs Acting on Central Nervous System (CNS)
Primidone
Structure:
HN
NH
O
O
Chemical name: 5-Ethyl-5-phenyl-1,3-diazinane-4,6-dione.
Uses: In partial and general seizures.
Formulation: Tablet.
Brand names: Mysoline, Resimatil, and Lepsiral.
Valproic Acid
Structure:
O OH
Chemical name: 2-Propylpentanoic acid.
Uses: To treat epilepsy and bipolar disorder.
Formulations: Tablet and Injectables.
Brand names: Vilapro, Valparin, and Epilim.
Gabapentin
Structure:
O
OH
NH
2
Chemical name: 1-(aminomethyl)cyclohexaneacetic acid.
Uses: To treat epilepsy and bipolar disorder.
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A Textbook of Pharmaceutical
Chemistry
Formulation: Capsule.
Brand names: Gabantin, Gabapin, and Neurontin
Approved New Drugs
Oxcarbazepine
Mechanism of action: It inhibits the voltage-gated sodium channels.
Levetiracetam
Mechanism of action: It modulates synaptic neurotransmitter release through binding to the
synaptic vesicle protein SV2A in the brain.
Rufinamide
Mechanism of action: It is a triazole derivative that prolongs the inactive state of voltage-
gated sodium channels.
Lacosamide
Mechanism of action: It inhibits the voltage-gated sodium channels. It is a medication for
the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain.
Stiripento
Mechanism of action: It enhances GABAergic inhibition and prolongs the open duration of
the GABA-A receptor chloride channel.
Retigabine
Mechanism of action: It acts as a neuronal KCNQ/Kv7 potassium channel opener which is
advantageous over other drugs.
Perampanel
Mechanism of action: It is a selective, a non-competitive antagonist of alpha-amino-3-
hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptor.
Nayzilam (midazolam) Nasal spray
Mechanism of action: It is used in the treatment of seizure clusters, which involve
potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site
of the GABA-A receptor and provide fast relief from seizure than other anti-epileptic drugs.
7.6 ANTIDEPRESSANT
Antidepressants are the drugs used in the treatment of major depression situations.
Depression (major depressive disorder or clinical depression) is a common but serious mood
disorder. It causes severe symptoms that affect how you feel, thinks, and handle daily activities,
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Drugs Acting on Central Nervous System (CNS)
such as sleeping, eating, or working. To be diagnosed with depression, the symptoms must be
present for at least two weeks.
It was proposed that depression is caused by the diminished formation of norepinephrine and
serotonin.
Some forms of depression are slightly different, or they may develop under unique
circumstances, such as:
(a) Persistent depressive disorder (Dysthymia) is a depressed mood that lasts for at least
two years. A person diagnosed with persistent depressive disorder may have episodes of
major depression along with periods of less severe symptoms, but symptoms must last for
two years to be considered a persistent depressive disorder.
(b) Perinatal depression is much more serious than the “baby blues” (relatively mild
depressive and anxiety symptoms that typically clear within two weeks after delivery)
that many women experience after giving birth. Women with perinatal depression
experience full-blown major depression during pregnancy or after delivery (postpartum
depression). The feelings of extreme sadness, anxiety and exhaustion that accompany
perinatal depression may make it difficult for these new mothers to complete daily care
activities for themselves and/or their babies.
(c) Psychotic depression occurs when a person has severe depression plus some form of
psychosis, such as having disturbing false fixed beliefs (delusions) or hearing or seeing
upsetting things that others cannot hear or see (hallucinations). The psychotic symptoms
typically have a depressive ‘theme,’ such as delusions of guilt, poverty, or illness.
(d) The seasonal affective disorder is characterized by the onset of depression during the
winter months when there is less natural sunlight. This depression generally lifts during
spring and summer. Winter depression, typically accompanied by social withdrawal,
increased sleep, and weight gain, predictably returns every year in seasonal affective
disorder.
(e) Bipolar disorder is different from depression but it is included in this list because
someone with bipolar disorder experiences episodes of extremely low moods that meet
the criteria for major depression. But a person with bipolar disorder also experiences
extreme high – euphoric or irritable – moods called ‘mania’ or a less severe form called
‘hypomania’.
Signs and Symptoms of Depression
Persistent sad, anxious, or ‘empty’ mood
Feelings of hopelessness, or pessimism
Irritability
Feelings of guilt, worthlessness, or helplessness
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A Textbook of Pharmaceutical
Chemistry
Loss of interest or pleasure in hobbies and activities
Decreased energy or fatigue
Moving or talking more slowly
Feeling restless or having trouble sitting still
Difficulty in concentrating, remembering, or making decisions
Difficulty in sleeping, early-morning awakening, or oversleeping
Appetite and/or weight changes
Antidepressant agents are classified as follows:
(a) MOA inhibitors (Monoamine Oxidase Inhibitors)
Moclobemide
Clorgyline
(b) SSR inhibitors (Selective Serotonin Receptor Inhibitors)
Fluoxetine
Sertraline
Citalopram
(c) Tricyclic antidepressant
(i) NA (Noradrenalin) + 5-HT (Hydroxytryptamine) receptor inhibitors
Imipramine
Amitriptyline
Doxepin
(ii) NA reuptake inhibitors
Desipramine
Nortriptyline
(d) Atypical antidepressant
Trazodone
Bupropion
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Drugs Acting on Central Nervous System (CNS)
Amitriptyline
Structure:
N
H
3
C
H
3
C
Chemical name: 3-(10, 11-Dihydro-5H-dibenzo[a,d]cycloheptane-5-ylidene)-N,N-
dimethylpropan-1-amine.
Uses: As an antidepressive agent.
Formulations: Tablet and Injectables.
Brand names: Elavil, Amline, and Sarotena
Imipramine
Structure:
N
N
Chemical name: 3-(10, 11-dihydro-5H-dibenzo-[b,f]azepin-5-yl)-N,N-dimethylpropan-1-
amine.
Uses: As an antidepressive agent.
Formulations: Tablet and Capsule.
Brand names: Depsonil and Tofranil
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Chemistry
Approved New Drugs
Vortioxetine
Mechanism of action: 5HT-3 antagonist with multimodal activity. It is a serotonin
modulator and stimulator because it has serotonin transporter (SERT) inhibition properties.
Vilazodone
Mechanism of action: It is a selective serotonin reuptake inhibitor (SSRI) partial agonist
and enhances the serotonergic activity in the CNS through selective inhibition of serotonin
reuptake.
Mifepristone
Mechanism of action: It is a glucocorticoid receptor antagonist.
L-milnacipran
Mechanism of action: It is a serotonin-norepinephrine reuptake inhibitor.
It affects the two neurotransmitters almost equally (3:1 norepinephrine to serotonin balance).
General Information
81
Chapter
Drugs Acting on
Autonomic Nervous
System (ANS)
The autonomic nervous system (ANS) is a division of the peripheral nervous system that
controls the internal organ system which functions largely unconsciously. It regulates body
functions such as heart rate, digestion, respiratory rate, pupillary response, urination and sexual
arousal.
8.1 SYMPATHOMIMETICS (ADRENERGIC AGENTS)
Drugs that produce an effect similar to that obtained by stimulation of the sympathetic
nervous system. Some of these predominantly act on the adrenergic alpha-receptors like
noradrenaline (norepinephrine) while others act on the adrenergic beta-receptors like
isoproterenol.
Adrenaline is produced in the medulla of adrenal glands as well as in some neurons of the
central nervous system. Within a couple of minutes during stressful situation adrenaline is quickly
released into the blood sending impulses to organs to create a specific response.
The sympathetic nervous system controls various important systems including
cardiovascular, bronchial airway tone, muscular tone, etc. It prepares the organ against the
conditions of stress, either of physical or physiological origin. Chemically they are monoamine
and are also called catecholamines. Mainly these substances contain an intact substituted amino
group and are hence also called sympathomimetic amines.
Adrenergic drugs do the following:
Increase blood pressure
Constrict blood vessels
Open the airways leading to the lungs
Increase heart rate
Stop bleeding
8
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A Textbook of Pharmaceutical
Chemistry
Catecholamines
Drugs that act on the adrenergic nervous system possess some chemical elements of the
endogenous agonist. Epinephrine, norepinephrine, and dopamine are the naturally occurring
catecholamines. Norepinephrine is a neurotransmitter present in the sympathetic nerves and the
brain. It also serves as a precursor for the synthesis of adrenaline in the adrenal gland.
Catecholamines are very prone to oxidation to produce orthoquinone-like compounds. The
development of pink-brown color is indicative of oxidative cleavage. Hence antioxidants such as
ascorbic acid or sodium bisulphite may be used to stabilize the solution of catecholamines.
Dopamine is a third naturally occurring catecholamine, acts as a neurotransmitter in the basal
ganglia of the CNS.
Bronchodilators
Bronchodilators open up the bronchial passages. These adrenergic drugs act on the beta
receptors directly. When they bind with beta-2 receptors, they cause the airways leading to the
lungs opening up. This helps improve breathing in patients with respiratory diseases such as
Asthma
Chronic Obstructive Pulmonary Disease (COPD)
Emphysema
Bronchitis
Examples of bronchodilator drugs include:
Albuterol
Formoterol
Levalbuterol
Salmeterol
Vasopressor Agents
Vasopressors act on the alpha-1, beta-1, and beta-2 adrenergic receptors. They also act on
dopamine receptors. These drugs stimulate smooth muscle contraction of the blood vessels. This
causes blood vessels to become narrow. This also in turn causes blood pressure to increase.
Increasing blood pressure can help to treat shock. Narrowing blood vessels can help stop bleeding.
It can also help keep anesthetics from spreading by closing off nearby blood vessels.
Certain vasopressors may also be used for treating colds or allergies. They shrink the swollen
blood vessels in the mucous membranes of the nose. These drugs are often referred to as nasal
decongestants.
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Drugs Acting on Autonomic Nervous System (ANS)
Examples of different vasopressors include:
Ephedrine
Epinephrine (Adrenaline)
Dopamine
Phenylephrine
Pseudoephedrine
Oxymetazoline
Cardiac Stimulators
Cardiac stimulators are used to stimulate and restore the heartbeat. They are used if the heart
stops beating suddenly because of electrocution, suffocation, or drowning. When this happens
epinephrine can be injected directly into the heart to help make it start beating again.
Sympathomimetic agents are classified as follows:
(a) Pressor Agents
Norepinephrine (Noradrenaline)
Ephedrine
Dopamine
Phenylephrine
(b) Bronchodilators
Isoprenaline
Salbutamol (Albuterol)
Terbutaline
Salmeterol
Formoterol
(c) CNS Stimulants
Amphetamine
Dexamphetamine
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Chemistry
(d) Nasal Decongestants
Pseudoephedrine
Phenylephrine
Naphazoline
Xylometazoline
Oxymetazoline
Adrenaline (Epinephrine)
Structure:
HO
O
H
NH
HO
Chemical name: (R)-4-(1-Hydroxy-2-(methylamino)-ethyl)-benzene-1,2-diol.
Uses: It is useful in the treatment of conditions including anaphylaxis (shock), cardiac arrest,
and superficial bleeding. It is a lifesaving drug available in ICU.
Formulation: Injectable.
Brand names: Adrena and Adrenaline.
Noradrenaline (Norepinephrine)
Structure:
HO
O
H
H
2
N
HO
Chemical name: (R)-4-(2-Amino-1-hydroxyethyl)-benzene-1,2-diol.
Uses: It is useful in the treatment of low blood pressure, glaucoma and migraine.
Formulation: Injectable.
Brand names: Norad and Adrenor.
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