Its helpful for m.pharm pharmaceutical chemistry students. in this topic cover antidepressant mechanism, symptoms, uses

1. CSJMUNIVERSITY KANPUR
UNIVERSITY INSTITUTE OF PHARMACY
ANTIDEPRESSANTS
PRESENTED BY
Shivam Kumar
M.Pharm 1st sem.
( Pharmaceutical chemistry )
SESSION 2019-20
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2. CONTENTS
 INTRODUCTION
 SYMPTOMS
 TYPE OF DEPRESSANTS
 MECHANISM
 CLASSIFICATION OF ANTIDEPRESSANT
 ADVERS EFFECT
 STRUCTURE ACTIVITY RELATIONSHIP
 REFERENCES
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3. DEPRESSION
Depression is a mental illness characterized by
pathological changes in mood, loss of intrest or
pleasure, feeling of guilt, disturbed sleep, sad, poor
concentration, suicidal thoughts.
It may be unipolar or bipolar disorder .
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4. SYMPTOMS
Markedly diminished intrest or pleasure
Significant weight loss/gain
Insomnia or hypertension
Agitation
Fatigue or loss of energy
Anxiety
Lack of concentration
Thought of suicide or death
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5. Types of depression
1.Major depression
Characterized by a combination of symptoms that interfere
with a person’s ability to work, sleep, study, eat, and enjoy
one’s-pleasurable activity. Major depression is disabling
and prevents a person from functioning normally.
2. Minor depression
Minor depression disorder is a type of depression with
milder symptoms than major depression . Criteria for the
diagnosis of minor depression suggest that a person must
experience at least 2 year.
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6. Mechanism of depression
Depression is associated with changes in the level of
neurotransmitters in the brain that help nerve cells to
communicate .E.x Serotonin , Dopamine, Nor
epinephrine
The level can be influenced by physical illness ,
genetics, substance abuse ,diet , hormonal changes,
brain injuries or social circumstances.
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7. STRUCTURE OF SYNAPES
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8. ANTIDEPRESSANTS
Antidepressants are the agent that are used in the
management and treatment of major depressive
disorder, All antidepressants drugs affects
monoaminergic transmission in the brain.
They are increase the level of monoamine in
brain.
Maine serotonergic neurotransmitter are involve.
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9. CLASSIFICATION
1. Reversible Inhibitors of MAO-A
2. Tricyclic Antidepressant
a. NA+5-HT Reuptake Inhibitors
b. Predominant NA Reuptake Inhibitors
3. Selective Serotonin Reuptake Inhibitor
4. Atypical Antidepressant
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10. 1. Reversible Inhibitor of MAO-A
MOCLOBEMIDE
Moclobemide inhibit the deamination of monoamine
neurotransmitters and increase the level of
monoamine (like serotonin, NA, dopamine ) on the
presynaptic .
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11. 2. Tricyclic Antidepressants
a. NA+5-HT Reuptake Inhibitors
1. Imipramine 2. Trimepramine
3. Clomepramine 4. Amitriptyline
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12. 5. Doxepine 6. Dothiepin
b. Predominant NA Reuptake Inhibitors
1. Desipramine
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13. 2. Nortriptyline
Tricyclic antidepressants inhibits the reuptake of
NA and serotonin on the synaptic cleft.
The tertiary amines inhibit the reuptake of NE as
well as 5HT, whereas the secondary amines are
relatively selective NE reuptake inhibitors.
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14. 3. SELECTIVE SEROTONIN REUPTAKE
INHIBITOR :-
1. FLUOXETINE 2. PAROXETINE
Used for the treatment of major depression anti anxiety
disorder
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15. 4. ATYPICAL ANTIDEPRESSANTS
1.TRAZODONE 2. AMINEPTINE
The antidepressant action of trazodone is dew to serotonin (5HT)
reuptake inhibitor and 5-HT2 receptor antagonistic action.
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16. ADVERSE EFFECTS
 Dry mouth
 Constipation
 Blurred vision
 Mydriasis (pupils dilate)
 Metallic taste
 Urine retention
 Sedation
 Weight gain
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17. S.A.R. OF TRICYCLIC ANTIDEPRESSANT
1. Variation in the side chain R :
a. For maximum antidepressant activity , the tricyclic
dihydrobenzazepine ring should be separated from
the basic N by three C propylene bridge.
b. Branching of propylene bridge by methyl substituent
does not affect activity eg. Trimipramine
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18. c. Tertiary amine is more potent inhibitor of serotonin
reuptake, while secondary amine derivative are more
potent inhibitor of nor adrenaline reuptake.
d. Derivative having tertiary amine has high affinity for
muscarinic , alpha1 – adrenergic and histaminergic
receptors
e. Larger alkyl group other than methyl or amine N, abolishes
activity and introduces toxicity.
2. Variation in ring substitution:-
Introduce of a choloro, substituent on 3 position of the
tricyclic ring does not affect antidepressant activity,
However 3,7 dichloro substitution abolishes activity.
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19. 3. Variation in the tricyclic ring:-
a. Replacement of ring nitrogen by carbon does not
affect antidepressant activity.
e.g.Amitryptyline,Nortryptyline,Doxepin , Dothiepin
b. Replacement of ring C at 10th position by O or S
does not affect activity .
eg :- Doxepine , Dothiepine
c. The exocyclic double bond at 5th position does not
affect activity .
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20. REFERENCES
1. Alagarsamy V. “textbook of medicinal chemistry”
edition 2010 vol.1, A division reed elsevier India
private limited, Page 219.
2. Vardanyan R.S. “Synthesis of essential drug”
edition 2006 vol. 1 , publisher Elsevier science 103.
3. Ransford Charles P. “A role for amine in the
antidepressant effect of a exercise” medicine and
science in sport exercise ,vol. 14, 1982, page 1-14.
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