Here we'll discuss about antipsychotic drugs and psychosis and also the structure, IUPAC name, MOA and uses of various drugs.

1. Antipsychotics agents
Presented by
Saroj kanta Bisoyi
Asst. professor
RCPHS,BAM

2. Introduction
• Antipsychotic are the drug that are used for
the treatment of pschosis.
• They act by producing specific sedative effects
and calm behavior in psychotic patient .
• Also called as neuroleptic drugs.
• These drugs have significantly stronger effect
on the CNS but they are not CNS Depressants.
• These drugs are antagonists of dopamine and
dopaminomimetics.

3. Mechanism of action
• Antipsychotic drugs are competitively bind
with dopamine receptors and block the action
of Dopamine on the coresponding receptors
(D1,D2,D3) sites and hence lower the
psychotic activity.
• These agents have the ability to change
behaviour also have other central and
peripheral effects.

4. C

5. Phenothiazine derivatives
• These are non selective and competative antagonists
of D1 and D2 receptors and hence blocks the action
of dopamine at the receptor sites.
• Also known as tricyclic
antipsychotics.
• They acts mainly on the CNS by producing moderate
sedation and antiemetic effects.

6. Classification of phenothiazine
• Based on the type of substitution on the N-
atoms of the phenothiazine ring
Sr.No
Substitution on the N-atom of the
phenothiazine ring
Ex of druugs
1
Phenothiazine with aliphatic side chain
Chloropromazine
Promazine
Triflupromazine
2 Piperazine derivatives
Acetophenazone
Fluphenazine
Perphenazine
Trifluoperazine
3 piperidine
Mesoridazine
Thioridazine

7. SAR Of phenothiazine
• Basic structure of phenothiazine ring .
1) Un substituted phenothiazine has no activity
but has good lipophilicity for brain penitration.
2) Substitution at C-2 and N-10 is required for the
activity.

8. SAR Of phenothiazine
3) C-2 must have electron withdrawing group and
terminal amino substituent must be present at N-
10 position of phenothiazine ring.It can be
piperazine/Piperidine/Aliphatic chain.
• Ex: Chlorpromazine and Prochorperazine

9. SAR Of phenothiazine
4) 4th position of the piperazine ring system can be
substituted by 2-Hydroxy methyl group to give
drugs with longer duration of action.
Ex- Perphenazine and Fluphenazine

10. SAR Of phenothiazine
• The linear alkyl chain linker between the core ring
and the terminal amino ring must have three
methylene units i.e- CH2-CH2-CH2-.
• Reduction in these three carbon number(n-propyl)
group reduces the activity.

11. SAR Of phenothiazine
At N-10 position the terminal substituent can be a part of piperidine
nucleus and substituent at C-2 can be methylthio(CH2S-) or its
oxidised form (CH3SO-) ex- Thioridazine and Mesoridazine

12. SAR Of phenothiazine
• The 10th position (=N-CH2) can be replaced
isosterically by ethylene group to form various
thioxanthenes.These are more potent than the
parent drug.
• Ex-chlorprothixene and thiothixine

13. • MOA:
 It act as antagonist of dopamine receptors,5HT-
Receptors,Muscarnic receptors as well as histaminic
receptors.
• Uses
1. In short term management of distrubuted and agitated
behavior.
2. As an antiemetic.
3. Used as antipsychotic due to its weak antipsychotic
activity.

15. Chloropromazine Hydrochloride
• MOA:
It acts as an antagonist of dopamine ,serotonin
,histamine,adrenergic and muscarnic receptors.
• Uses
1. Treatment of psychotic disorder such as
schizophernia.
2. As an antiemetic to control nausea and vomiting.
3. Used in treatment of migraine.
4. Relief of interactable hicup (involuntary
movement of diaphragm)
5. As a part of tetanus treatment.

16. • MOA:
Action similar to Chlorpromazine.
• Uses
1. Treatment of Psychosis disorder.

17. • MOA
It act as antagonist for dopamine and adrenergic
receptors.
• Uses
1. Treatment of psychosis.
2. To control distributed and agitated behaviour.
3. Little antiemeic activity.

18. • Correct IUPAC NAME: 1- [10-[3-[4-(2-hydroxyethyl)piperazin-1-
yl]propyl]phenothiazin-2-yl]ethanone
• MOA
 It blocks D2 –dopamine receptors hence it act as an dopamine antagonist.
• Uses
 Treatment of schizophernia.
 Antipsychotic prodrug & used in the treatment of psychosis.

19. • MOA
 It block dopamine receptors especially D2 receptors.
 It also block anticholinergic and alpha adrenergic receptors.
• Uses
1. As antiemetics in treatment of nausea,vomiting and
vertigo.
2. Typical antipsychotic.
3. More potent than chlorpromazine and hence used in the
treatment of migraine headaches.

20. • MOA
Act as an antagonist of dopamine receptors.
• Uses
1. Treatment of schizophrenia.
2. Also efective in generalized anxiety disorder.
3. Severe nausea and vomiting.

21. Ring analogues of phenothiazines
• MOA
 It is an antagonist of dopamine ,muscarnine,adrenergic
and histamine receptors.
• Uses
1. Treatment of schizophrenia and acute mania disorder.
2. Antiemetic effect.
3. Treat anxiety and insomnia.

22. • IUPAC Name: (9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-
yl)propylidene]-9H-thioxanthene-2-sulfonamide
• MOA
1. It is a highly potent antagonist of dopamine receptor.
2. It also act as antagonist of adrenergic,histamine and serotonin
5-HT receptors.
• Uses
1. Treatment of schizophrenia and bipolar mania.
2. Reduces aggression and desire to hurt yourself and other.
3. Help to decrease hallucination.

23. ;/
• IUPAC Name: 8-chloro-6-(4-methylpiperazin-
1-yl)benzo[b][1,4]benzoxazepine
• MOA
It is a dopamine or serotonin 5 HT2 blocker.
• Uses
1. Acute agitation with schizophrenia or bipolar
disorder in adults.

24. • IUPAC Name:8-Chloro-11-(4-methylpiperazin-1-
yl)-5H-dibenzo[b,e][1,4]diazepine
• MOA
It is an antagonist of dopamine and serotonine
receptors.
• Uses
1. Typical antipsychotic used in treatment of
schizophrenia.

25. SAR Butyrophenones
• The main proto type of the drug in the
category is haloperidol
• It is the standard antipsychotic drug and
various changes have been made in its
structure to give drugs with better action and
fewer side effects.

26. SAR Butyrophenones
• If fluorine is replaced by other group it will lower
the activity.
• The presence carbonyl group is required for the
activity.
• Replacement of (=C=O) by other isosteric group
like –CHOH,-O-,-S- etc.reduced the potency of
the drug.
• Increase or decrease in the length of the propylene
bridge decreases the activity.
• Various substitutin at 4th position of piperidine
ring by other ring increases the potency of the
drug.

28. • IUPAC Name: 4-[4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl]-1-
(4-fluorophenyl)butan-1-one2
• MOA
 It competatively blocks dopamine receptors and has some effects on
5HT and α receptors.
• Uses
1. Antipsychotic used in treatment of schizophrenia.
2. Severe anxiety and for nausea and vomiting during radiation
therapy for cancer.
3. To control adjunctive treatment of alcohol and opiod withdrawl.
4. In neurological disorder like tourette syndrome ( neuropsychiatric
disorder with onset of children).

29. • MOA: same as haloperidol.
• USES
1. As an antipsychotic antiemetic.
2. As sedative in intensive care treatment as it
depress CNS.

30. • MOA
It act as antagonist of dopamine ,serotonin,
α1 –adrenergic and histamine receptors.
• Uses
1. Schizophrenia and other psychosis disorder.

31. Beta amino ketone
• MOA
 Molindone act on D2 receptor and decreases dopamine activity.
 It has low to moderate affinity towords cholinergic and alpha-
adrenergic receptors.
• Uses
1. Schizophrenia and other psychosis disorder.

32. Benzamides
• MOA
 It is selective and acts as a D2 dopamine receptors
antagonist.
• Uses
1. Treatment of schizophrenia, vertigo and anxiety
disorder.