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Antipsychotics

Presented By:
Mr. Kiran D. Baviskar,
Assist. Professor
Dept. of Pharmaceutics,

Smt. Sharadchandrika Suresh Patil College of Pharmacy, Chopda.


Antipsychotics used to treat psychoses like schizophrenia,
mania, sensile dementia and behavior disorders. These drugs
act by depressing CNS (decreasing dopamine level) by
producing sedation without producing sleep.

Clinically, these agents counteract or minimize hallucinations


and delusions, alleviate psychomotor excitement, and facilitate
social readjustment.

Antipsychotics are also known as neuroleptics (formerly


ataractics and major tranquillizers) .
Psychosisis a severe mental illness leading to impairment of
thoughts. A psychotic disorder is usually characterized by
withdrawal from reality and its symptoms are divided into two
types:
 Positive and
 Negative.
Positive psychosis symptoms include
(i) auditory-, visual-, tactile, gustatory-hallucinations,
(ii) delusions,
(iii) disorganized thought and speech, and
(iv) disorganized behavior.
Negative psychotic symptoms include
(i) decrease or complete loss of the ability to emotionally
respond to people,
(ii) decrease in speaking, and
(iii) difficulty sticking with activities and tasks (abolition), for
instance getting dressed in the morning.

Positive psychosis symptoms are exceedingly first associated


with schizophrenia (abnormal social behavior and failure to
respond to reality) and then with post-traumatic stress
disorder.
Antipsychotic drugs (also called neuroleptics) are primarily
used in the therapy of psychoses, including schizophrenia,
organic psychoses, the manic phase of manic-depressive
illness and other acute or chronic idicpathic' psychotic
illnesses.
Antipsychotics are not CNS depressants.
Nuclear neuroimaging findings suggested that psychiatric
patients correspond to increased dopamine level in brain.
Therefore, drugs inhibiting dopaminergic
neurotransmission have been clinically used in the
management of several neurological and psychiatric
disorders.
Antipsychotics are mainly classified as follows:

Phenothiazine derivatives- Chlorpromazine, Fluphenazine

Thioxanthene derivatives- Chlorprothixene

Dibenzazepines- Loxapine, Clozapine

Butyrophenons- Haloperidol, Droperidol


Dihydroindolones- Molindone, Oxypertine

Diphenylbutylpiperdines- Pimozide, Penfluridol

Benzamide -Sulpiride, Clebopride

Miscellaneous.
SAR of Antipsychotics:
Phenothiazines are the derivatives of phenothiazine tricyclic
heterocyclic moiety. The central ring possesses nitrogen and
sulphur heteroatoms.

1.Substitution at the second position of phenothiazine nucleus


by electron withdrawing substituent increases antipsychotic
activity. Ex: Chlorpromazine (chlorine).

2. Substitution at the 3-position of phenothiazine nucleus


increases antipsychotic activity than unsubstituted derivatives
but not by substitution at 2-position.

3. Substitution at 1 and 4 positions of phenothiazine nucleus


reduces the antipsychotic activity.
4. Phenothiazines must have a nitrogen-containing side-chain
substituent on the ring nitrogen for antipsychotic activity. The
ring and side-chain nitrogen must be separated by a three
carbon chain.

5. The side chains are either aliphatic, piperazine, or piperidine


derivatives. Piperazine side chains confer the greatest potency
and the highest pharmacological selectivity.

6. Fluphenazine and long chain alcohols form stable, highly


lipophilic esters, which possess markedly prolonged activity.
7. Substitution on the side chain with a'large or polar group
such as phenyl, dimethylamino or hydroxyl results in loss of
tranquilizing activity.

8. Side chain containing N-atom should be tertiary for


optimum activity. The two methyl group gives maximum
activity but if anyone of them derivatised cause decrease in
activity.

9. Side chain containing 3 carbon atoms gives neuroleptic


activity whereas 2 carbon atom chain shows antihistaminic
and anticholinergic activity.