Drugs acting on CNS

Mental disorders
The mental disorders can be classified as follows –
 Neuroses: It refers to the mental disorders which doesn’t affect a
person’s conception of reality. Basically mental disorders falling
under neuroses may affect personality, mood and to a limited
extent behavior but such disorders doesn’t prevent the patient from
most of the normal activities.
 The term neurosis (or neuroses) is no longer used by medical
practitioners but nevertheless this term is widely known. This term
was then used to indicate disorders such as anxiety disorders,
phobias, obsessions and compulsions etc.
 Psychoses: Psychoses refers to those mental disorders which are
characterized by distorted or non-existent sense of reality.
Mental Disorders(Cont.)
 Mental Disorders(Cont.)
• The most important thing to note about these
disorders is that we don’t fully know the
pathophysiology of these diseases. The
pathophysiology is inferred from the mechanism of
action of the psychoactive compounds seen to be
useful in the treatment of these disorders.
 Description of different mental disorders
Disease Description Treatment strategy
Anxiety is fear and discomfort accompanied by Anxiety is treated with anxiolytic drugs.
autonomic response. Such fear and discomfort results Anxiety is treated with –
from a situation that makes the patient feel threatened 1. Benzodiazepines
in any way. Anxiety is a normal response and of short 2. SSRI
duration for normal people. But if anxiety is unfocused 3. 5-HT and NA reuptake inhibitors
or out of scale with perceived threat then treatment is 4. TCA
required. In such case – 5. β-Blockers etc.
1. Increased muscle tension
2. Autonomic nervous system dysfunction
3. Irritability
Anxiety 4. Fatigue
5. Sweating
6. Dry mouth
7. Palpitations
8. Loss of appetite
9. Headache etc. are seen.
 Description of different mental disorders(Cont.)
Disease Description Treatment strategy
Hysteria is a mental disorder where Rest and assurance are probably the
patient develops physical symptoms best treatment strategy. If drugs are
due to psychological conditions. given then anxiolytics may be given.
Basically the patient creates his/her
own illness to escape from an
Hysteria/ unpleasant situation.
Conversion disorders The symptoms of hysteria are –
1. Emotional instability
2. Sensory disturbances
3. Loss of motor function etc.

It is also known as obsessive- Drugs like chlorimipramine and

compulsive disorder (OCD). In this fluoxetine have been used which are
case, the patient’s life is restricted by anxiolytic.
his irrational obsessions. For example ─ Behavior therapy
Obsessional neurosis thinking that he/she is dirty and washing
over and over again. Such obsessions
take up a significant portion of his/her
time.
 Description of different mental disorders(Cont.)
Disease Description Treatment strategy

Depression is a mood disorder where The modern treatment of depression

the patient feels misery and loss of usually uses SSRI. Older treatment
pleasure. It is a prolonged abnormal strategies used TCA and MAO which
response to a stressful situation that are still in use but use has decreased.
Depression
leaves the patient feeling sad, unhappy
and wary.

Mania is basically abnormally - Lithium carbonate (most important

excessive excitability. It is the opposite and effective)
of depression. It’s symptoms are – - Antipsychotics
- Euphoria/elation - Anticonvulsants
- Restlessness
Mania - Lack of sleep
- Increased energy
- Impulsivity etc.
 Description of different mental disorders(Cont.)

Disease Description Treatment strategy

Also known as bipolar disorder. It is - First line drug is lithium carbonate

disorder having two opposite poles – - Anticonvulsants e.g.
mania and depression. Half the time carbamazepine and valproate.
the patient is manic and then other time
depressed.
Manic depressive disorders

Psychotic disorder characterized by

emotional disturbances or mood
disorder such as depression or mania.
Affective psychosis Lithium and TCAs
 Description of different mental disorders(Cont.)
Disease Description Treatment strategy
When psychiatric disorder is due to
organic causes i.e. when it is not
attributed to problems of the psyche
rather problems of physiologic or
Psychiatric organic states
medical functioning in the body, it is
called organic psychic disorders.

Schizophrenia is a psychiatric disorder

characterized by abnormal social
behavior and loss of sense of reality.
When the psychiatric disorder affects
Schizophrenia Antipsychotics.
the normal functioning of the patient
then it is schizophrenia.
 Classification of psychotropic drugs

• Antidepressants
– SSRI
– MAOI
– TCA
– TECA
– NSRI
– NDRI
• CNS Stimulants
– Amphetamines
– Rauwolfia alkaloids
• Antipsychotics
– Phenothiazines
– Butyrophenones
– Thioxanthines
 Classification of psychotropic drugs
• Mood stabilizers (antimanic drugs)
– Lithium carbonate
– Lithium citrate
– Carbamazepine
• Antianxiety drugs
– Older drugs
• Ethanol
• Barbiturates
• Diphenyl methane derivatives
• Propanediols
– Newer drugs
• Antipsychotics
• Benzodiazepines
• β-blockers
• TCAs
 Antipsychotic Drugs
1. Phenothiazines:
• General structure:

No. Name R1 R2 Activity

(CH2)3 N CH3
1 Promazine (Antiemetic) H
CH3

2 Chlorpromazine −Cl Highly active

3 Flupromazine −CF3 Extrapyramidal effects

 Antipsychotic Drugs
Mechanism of action:
These drugs block the D2 receptors of brain and decrease the normal effect of dopamine
release. Blocking the D2 receptor in the mesolimbic pathway results in the antipsychotic effect.

Clinical use of chlorpromazine:

• Symptomatic treatment of acute schizophrenia. Daily dose up to 1000mg.
• Manic and hypomanic symptoms associated with some other psychotic conditions usually
respond well.
• Withdrawal symptoms of alcohol & barbiturates are treated by this drug.
• Amphetamine intoxication produces a state similar to schizophrenia. Used in amphetamine
poisoning as anti dopaminic agent.
• Prevents or relieves vomiting caused by other drugs.
• Employed to induce sleep of mental patient.
• As preoperative sedative and for the production of hypothermia.
 Antipsychotic Drugs
• Extrapyramidal side effects of chlorpromazine therapy—
• Motor restlessness, uncoordinated movement, increased
muscle tone, tremor & immobility of facial expression.
• Chlorpromazine causes lethargy & somnolence in 1st use &
don’t usually persists. Large dose may produce confusion &
disorientation.
• Dry mouth, blurred vision, paralytic ileus, mega colon, urinary
retention & glaucoma.
• Obesity is a common side effect of continued chlorpromazine
therapy.
 Antipsychotic Drugs
2. Butyrophenones:
• General structure:

No Name R Dose

OH
N
3-10 mg in
1 Haloperidol
schizophrenia

Cl

OH
N

2 Trifluperidol 1-5 mg
CF3
 Butyrophenones
• Mode of action (Haloperidol):
• On CNS: Haloperidol includes sleep in excited patients by CNS effect,
less prominent effect than chlorpromazine. Lower convulsive threshold.
Dopeminergic blockade same with chlorpromazine. It also blocks
apomorphine induced emesis and little anticholinergic activity. It blocks
activation of α-receptors by sympathomimetic amines.
• On CVS & respiratory system: Hypotension observed. Respiratory
depressant action.
• Endocrine effects: Weight gain doesn’t seem to be a side effect of
haloperidol. Other effects are same with phenothiazines.
 Antidepressant Drugs
• Classification:
• Monoamine oxidase inhibitors
– Hydrazine derivatives
– Others
• Drugs that inhibit the reuptake of monoamines at synapse
– Imipramine like tricyclic compound
– Other reuptake inhibitors
• Drugs with novel action on monoamine systems
• Drugs directly related to the monoamines
– Amphetamine & other sympathomimetic agents
– Tryptophan & 5-HT
– Dihydroxyphenylalanine (DOPA)
 Monoamine oxidase inhibitors (MAOI)
 Hydrazine derivatives
• General structure:

No Name R1 R2 Daily dose(mg)

CH2CH2 15-60 then

1 Phenelgine H
10-30
 Monoamine oxidase inhibitors (MAOI)

No Name R R Daily dose(mg)

O CH3
100-150 initial,
2 Iproniazid N C CH
25-30 maintenance
CH3

O CH3
H2
3 Pivazide C C C CH3 Withdrawn
CH3
Mechanism of action of MAO Inhibitors
 Monoamine oxidase inhibitors (MAOI)
• Side effects:
• Causes severe liver damage as a result of lowering organ’s
resistance to viral infection.
• Pheniprazine also causes red-green color blindness,
sometimes irreversible.
• Automatic disturbances (postural hypotension, dry mouth,
sweating, constipation, and diarrhea) occur.
• Other toxic reactions of CNS include headache, dizziness,
and muscle weakness, restlessness, seriously agitated.
 Tricyclic antidepressants
• General structure:

No Name R1 R2 Daily oral divided Uptake

dose (mg) preferentially
inhibited

CH3

1 Imipramine CH2CH2CH2 N H 75-200 ST > NA

CH3

CH3
2 Chloripramine CH2CH2CH2 N −Cl 50-200 NA

CH3
Mechanism of action
 Tricyclic Antidepressants
Uses:
Tricyclic antidepressants are approved by the Food and Drug Administration (FDA) for treating
several types of depression, obsessive compulsive disorder, and bedwetting. In addition, they
are used for several off-labels (non-FDA approved) uses such as:
• Panic disorder,
• Bulimia,
• Chronic pain (for example, migraine, tension headaches, diabetic neuropathy, and post
herpetic neuralgia)
Side effects:
• Blurred vision,
• Dry mouth,
• Constipation,
• Weight gain or loss,
• Low blood pressure on standing,
• Rash,
• Hives, and
• Increased heart rate.
 Antianxiety Drugs
• Benzodiazepines:
• General structure:

Name R1 R2 R3 R4 R5 Daily dose (mg)

Diazepam −Cl −CH3 O H2 - 5-50

Nitrazepam −NO2 H O H2 - 2.5-10 (h)

Lorazepam −Cl H O −OH −Cl 2-3

Clonazepam −NO2 H O H2 −Cl 5-10

Mechanism of Action
 Benzodiazepine
 Diazepam
 Uses:
• Pronounced anticonvulsant properties.
• Drug for the control of status epilepticus (IV administration). IV diazepam is anesthetic.

 Nitrazepam
 Uses:
• More pronounced hypnotic action than other Benzodiazepine & proved to a useful
replacement for the barbiturate hypnotics.

 Flurazepam & Fluxitrazepam

 Uses:
• Benzodiazepine hypnotics, advantageous than nitrazepam, hangover & dependence liabilities
prove to be minimal.
• Also used as anesthetic induction agent.
 Benzodiazepine
 Clonazepam:
 Uses:
• Achieved considerable success as an antiepileptic drug.
• Also applied in tardive, dyskinesia (purposeless movement, chewing, smacking the lips,
movement of the arms, legs & pelvis)

 Side Effects:
• Drowsiness
• Confusion
• Dizziness
• Trembling
• Impaired coordination
• Vision problems
• Grogginess
• Feelings of depression
• Headache
 CNS Stimulants
• Amphetamines:

• Mechanism of action:
• Amphetamine act by increasing release of dopamine from
nerve terminals. Amphetamines are thought to enter the
nerve terminal via the transporter, disrupt storage vesicles
of dopamine and reverse the direction of the dopamine
transporter through which large amounts of dopamine are
released. It also blocks the reuptake of norepinephrine and
dopamine into the presynaptic neuron.
 CNS Stimulants
 Use:
• Amphetamine activates receptors in the brain and
increases the activity of a number of neurotransmitters,
especially norepinephrine and dopamine.
• Dopamine is associated with pleasure, movement, and
attention.
• In the past, it has been used to treat narcolepsy (excessive
daytime sleepiness) and to help with weight loss, but this is
less common now.
 Dose:
• Usual Adult Dose for Narcolepsy is 5 to 60 mg orally per
day in divided doses. For obesity, 5 to 10 mg orally 30 to
60 minutes before meals.
 CNS Stimulants
 Side effects:
• Low or high blood pressure
• Rapid heart rate
• Abdominal pain
• Loss of appetite, nausea, and weight loss
• Blurred vision
• Dry mouth
• Nose bleed
• Nasal congestion
Thank You