Tranquilizers

1. A tranquilizer is a drug that acts on the CNS and is used to calm, decrease anxiety, or help a person
to sleep. Often called depressants because they suppress the CNS and slow the body down. Used to
treat mental illness that are characteristic of the psychoses which is a behavioral disorder. Also used in
common anxiety and sleeplessness. Can cause dependence and certain ones can easily be abused.
Minor tranquilizers are called anxiolytics and major tranquilizers are called Antipsychotics.

2. Psychoses eg Schizophrenia Affective disorders eg Depression and Mania

3. False perceptions (Hallucinations) False beliefs (Delusions)

4. Emotional disturbances: Mood is very low (Depression) Mood is very high (Mania)

5. Most common form of psychosis (1% of world population) Most typical features are : -Delusions -
Hallucinations -Disorganised thinking -Emotional abnormalities

6. Psychosis: The psychosis are inhibition of mood and emotional responses. Psychiatric illness can
be divided into neurosis and psychosis. Neurosis is a class of functional mental disorders involving
distress but neither delusions nor hallucinations. Neurosis may also be called psychoneurosis or neurotic
disorder. The psychotic patient have difficulty in understanding reality and their own conditions, they
live in a world of his own. They experience hallucinations and delusions (paranoid in nature), thought
disorders and withdrawal from social contacts and flattering of emotional responses.

7. An excess in dopaminergic signaling is hypothesized to be linked to the positive symptoms of

psychosis, especially those of schizophrenia. Many antipsychotic drugs accordingly target the dopamine
system

8. I. First generation 1) Phenothiazine derivatives: Chlorpromazine HCl, Triflupromazine, Thioridazine

HCl, Mesoridazine HCl, 2) Butyrophenones: Haloperidol, Droperidol, Resoperidone. 3) Thioxanthenes:
Flupenthixol, Clopenthixol, Zuclopenthixol. II. Second generation Aripiprazole, Clozapine, Zotepine,
Olanzapine, Risperidone, etc. Classification

9. Chlorpromazine Haloperidol Fluphenazine Perphenazine Thioridazine Prochlorperazine Structures of

some antipsychotics

10. I. Modification in tricyclic systems: a) Most of the compounds have either a six membered central
ring (6-6-6). (Example : phenothiazine) classes for good antipsychotic activity. b) Compounds having
larger central ring (Eg. Imipramine 7- membered) and smaller central ring, Eg. carbazole (5 membered
ring) are lack in antipsychotic activities and produce only antidepressant activity). c) Analogues of
tricyclic compounds that lock a central ring (Eg. Rimozide) generally devoid of antipsychotic activity. N S
R10 R2

11. b) Introduction of methyl group at position 1, 2 or 3 of 3 – amines propyl side chain decreases the
antipsychotic activity and may result Imipramine like activity. c) Bridging of position 3 of side chain to
position 1 of phenothiazine nucleus reduces neuroleptic activity. SAR for Phenothiazine derivatives N S
R10 R2II. Modifications of alkyl side chain at R10: : a) The maximum potency is obtained when the
nitrogen of phenothiazine and basic amino group is connected by a three carbon side chain, because it
permits maximum resemblance with that of most preferred conformational form of dopamine.
12. a) Maximum neuroleptic potency is obtained in amino alkyl substituents having 3° amines group
than 2° and 1° amines group containing compounds. b) Alkylation of basic amino group with groups
larger than methyl group decreases neuroleptic potency. Example: Diethylamine analogues. c)
Replacement of dimethylamine group with Pyrrolidine, morpholine groups decreases the neuroleptic
potency. d) The activity is retained or increased if the amino group is replaced with piperidyl or
Piperazine groups. Example : Mesoridazine, carphenazine. SAR for Phenothiazine derivatives N S R10
R2III. Modifications of basic amino group:

13. e) Bridged piperidine derivatives retains the neuroleptic activities. f) Introduction of hydroxyl,
methyl, hydroxy-ethyl groups to piperidine and Piperazine moieties increase the potency. g) N4-
Piperazine substituents with phenyl ethyl, p – amino phenyl ethyl or estirified long chain fatty acids
increases the activity. SAR for Phenothiazine derivatives N S R10 R2III. Modifications of basic amino
group:

14. a) Substituents at position 2 is optimal for neuroleptic potency. b) 2–substitution is an electron

withdrawing group increases the neuroleptic activity, the potency increases in the following order OH <>
c) Oxidation of sulfur at 5 – position decrease the neuroleptic activity. d) 1-Azo phenothiazine is more
potent than parent compound. Example: Prothipendyl. SAR for Phenothiazine derivatives N S R10 R2IV.
Phenothiazine ring substituents at R2: Prothipendyl

15. Mechanisms of action -competitive blockade of dopamine receptors and serotonin receptors -
adverse effect result from blockade of different receptors

16. Chlorpromazine 2-Chlorophenothiazine 3-Chloropropyl- dimethylamine

17. Prochlorperazine 2-Chlorophenothiazine

18. Chlorpromazine, Fluphenazine, Thioridazine, Trifluoperazine Similar therapeutic effects

Different potency and side effect Chlo. And Thio. lower potency, more autonomic side effects and
fewer extrapyramidal side effects than high potency Flu. Higher potency

19. Blockade of D2 receptors Positive symptoms of Sch. Decrease in 1-3 weeks Less agitated, fewer
auditory hallucinations, disappear of paranoid delusions Behavioural improvement