This document discusses antipsychotic/neuroleptic drugs used to treat psychosis and schizophrenia. It covers: 1. The etiology and symptoms of conditions treated, including schizophrenia, psychosis, and bipolar disorder. Positive symptoms respond to treatment while negative symptoms are less responsive. 2. The proposed neurochemical bases involving dopamine, serotonin, and glutamate systems. Antipsychotics work by blocking dopamine D2 receptors in the brain. 3. Details of typical antipsychotics including phenothiazines, butyrophenones, and thioxanthenes. Newer atypical antipsychotics like clozapine, risperidone, and olanzapine are also mentioned

1. Antipsychotics/Major Tranqullizers/Neuroleptics
or
Anti-schizophrenic drugs
• Psychosis
1. Schizophrenia
2. Organic Psychosis
3. Affective disorders
– Depression
– Mania
– Manic depressive illness (bipolar
depression)

2. • Etiology:
• Not known
• Strong but incomplete genetic pre-
disposition
• (1st degree relatives – 10%)
• (2nd monozygotic twin – 50%)
• suicide is about 10% cases

3. • Symptoms:
• 1.Positive symptom: (result from
Neurochemical Abnormality)
• Increase do paminergic transmission
Respond well to Rx
• Delusions often paranoid in nature:
cann’t be rectified by reasoning

4. • Hallucinations:
• They may be
• Visual
• Auditory
• Tactile (CD Canine bugs)
•

5. • c) Thought disorder
• Wild train of thoughts
• Draw irrational conclusion with the feeling
that thoughts are inserted or withdrawn by
an outside agency.
• Usually not like to be interfered, flight of
ideas from one thought to other thought.
• Broadcast of ideas.
• d) Abnormal stereotypical behavior,

6. • 2. Negative Symptoms:
•
• Result from brain atrophy
• Don’t respond / less responsive to R x
• Emotional blunting.
• Poor Socialization
• Cognitive deficit (Dementia)
• more irritable.

7. • Neurochemical Basis:
• 1) Dopamine Theory (Hypothesis by
Carlson awarded noble prize in
year 2000)
• Dopamine hyperactivity in mesolimbic
and mesocortical pathway & amygdale
positive symptoms of schizophrenia.
• Proof:
• Dopamine agonists – produce these
symptoms of schizophrenia e.g. central

8. • 2) Glutamate Theory
– Glutamate and DA exert excitatory and
inhibitory effects respectively on GABA ergic
striatal neurons which project to thalamus and
constitute “sensory Gate”
– Glutamate or DA disables the gate and
uninhibited sensory input reaches the cortex.
– Glutamate NMDA (N-methyl deaspartate)
recep antagonists:
• Phencyclidine

9. • 3) 5 – HT Theories:
• 5 – HT dysfxn
• LSD & 5-HT2 Receptors agonists produced
schizophrenia like syndrome.
•
• Mostly of Anti-psychotics in addition to
affect dopamine also back serotonin
receptors.

10. • 4) Current views:
• Combination of DA hyperactivity with 5-
HT & glutamate dysfxn.

11. • 1) Nigrostriatal Pathway:
• 75% of dopamine in brain
• 2) Mesolimbic mesocortical pathway:
• Projects from neurons near S.N to
limbic system & Neocortex
• Behaviorial effects
• Hyperactivity leads to schizophrenia.
• 3) Tuberoinfundibular (Tubrohypophy
Scal) Pathway:

12. • 4) Medullary Perventricular Pathway:
• From neurons of Motor Nucleus of Vagus
___ Periventricular nuclei
• Eating behavior
• Satiety center ____ Bolimia Nervosa
• Appetite Cetre _____ Anorexiz Nervosa
• 5) Incertohypothalamic Pathway:
• From medial zone incerta to
hypothalamus & Amygdala.

13. • 5) Incertohypothalamic Pathway:
• From medial zone incerta to
hypothalamus & Amygdala.
• Sexual drive, Microvasculatory function
and temperature regulation.
• 6) Many local Dopaminergic Neurons in
olfactory cortex & retina:
• 7) Dopaminergic transmission in
periphery:

14. Classification of Antipsychotic
Drugs
A: Classical / Typical Antipsychotics.
I. Phenothiazine Derivatives
a. Aliphatic compounds
Chlorpromazine
Promazine.
b. Piperazine Compounds:
Procholorperazine
Perphenazine
Fluphenazine
Trifluperazine
c. Piperidine Compounds:
Thioridazine 
Mesoridazine

15. • A) Classical Typical Nemoleptics:
• 1. Phenothiazines:
• a) Aliphatic Comp
• (less potent,sedation & weight gain)
• Chloropromazine (Largactil)
• Promazine
• Triflupromazine

16. • b) Piperidine Derivative:
• Thioridazine (Melleril, less potent, Anti-Cholinergic)
• Mesoridazine (metabolite of thioridazine)

17. • c) Piperazine Derivative:
• Fluphenazine (I/V preparation, slowly, release,
• Perphenazine
• Trifluperazine
• Prochlorperazine
• Thioperazine .

18. • 2. Thioxanthines: (also available as
DEPOT preparation)
• Thiothixene
• Clopenthixol
• Flupenthixol
• Chlorprothixine

19. • 3. Butyrophenones:
• Haloperiodol
• Properidol
• Benperidol

20. • B) Atypical Neuroleptics:
• Their mechanism of action is different
from anti-psychotics
• Loxapine
• Clozapoine (Clozanl) ___ A/E: Cause
agranulocyctosis ___ Bone marrow
depression

21. • Risperidone ____ commonly used D2 5HT2 selective
activity for D4 receptors
• Olanzapine __ Disadv: cause agranulocytosis
• Ziprasidone(patients resistant to other drugs. Also Rx of negative
effects)
• Sulpirdie (D2 selective)
• Remazopride
• Remoxipride
• Pimozide (D2 selective) long acting indole
• Quetiapine
• Aripiprazole

22. II. Butyrophenone Derivatives
 Haloperidol  Droperidol
III. Thioxanthenes
 Thiothixene  Flupenthixol
IV. Rauwolfia Alkalois
 Reserpine

23. B. Newer / Atvpical Antipsychotics
Miscellaneous Structures.
 Clopazine  Olanzapine
 Quetiapine  Pimazole
 Pimazole  Sulpiride
 Risperidone
C: Drugs used for Manic-Depressive
Disorders:
 Lithium carbonate

24. Phenothiazines
• Chemistry & Structure
• Pharmacokinetics

25. MOA
Act on a variety of CNS & Peripheral receptors
– Post synaptic D2 receptor blockade
– 5 HT2 receptor blockade
– Muscarinic receptor blockade
– Ganglion blockade
– Quinidine like effects
– Alpha-1 adrenergic blockade
– Local anaesthetic like activity

26. MOA of Antipsychotic effect:-
Acts by blocking Post Synaptic D2 receptors
in Dopaminergic pathways in CNS.
Three important Dopaminergic pathways
• Mesolimbic mesocortical pathway
• Nigrosticatad pathway
• Tuboinfundibuar pathway
Additional Pathways
• Medullary periventricular pathway
• Incertohypothalamic pathway

27. Dopamine Receptors

28. Ph. Actions
• a) PTS:
• No loss of intellectual functions and
performance (clear sensorium)
• Alteration of deranged thought process
• Emotional quietening
• Psychomotor slowing
• Antagonism of behavior eff. of amphetamine
• Decreased paranoid idea
• Decrease initiative
• Decrease aggressiveness

29. • b) NORMAL (NON -PSYCHOTICS)
• unpleasant feelings due to
• Sleepiness, restleseness
• Autonomic effects : b/c of muscarinic
blockade
• unpleasant feelings due to
• Sleepiness, restleseness
• Autonomic effects : b/c of muscarinic
blockade

30. 2. Effect on motor activity
a. Decreased spontaneous activity
b.Extra Pyramidal symptoms
• Parkinsonism
• Acute dystonias
• Neuroleptic malignant syndrome
• Akathisia
• Tardive Dyskinesia
• Perioral tremor (Rabbit syndrome)

31. • ) DECREASE SEIZURE THRESHOLD:
• Convulsive potential
• High dose: cause convulsion cause
seizure in patients of epilepsy
• Aggrevate epilepsy
• If anti-epilepsy is taken by epilepsy potent,
he has to increase the dose
• Potentiate cause of seizure latent epilepsy
patient

32. 6. Effect on CTZ
7. Endocrinal Effects
8. Hypothermia/ Hyperthermia

33. • a) ANTICHOLINERGIC
• b) ADRENOCEPTORS BLOCKADE
• Orthostatic hypotension
• Less less with halo oeriod of flupenthixol
and eluphenazine and other non
phenothiazines except clozapine
• c) WEAK GANGLIONIC BLOCKADE:
• Both symp and P/symp ganglionic
blockade . Non blockade cz transmission

34. B: PERIPHERAL EFFECTS
1. Effect on ANS
2. Effect on CVS
3. Quinidine like anti-arrhythmic effect on heart
4. Miscellaneous
– LA effect
– Renal effects
– Effect on Liver
– Antihistaminic action
– Skeletal muscle relaxant effect

35. • v) RESP. CONTROL:
• Depressant effect
• No permanent effect in N individual
• No prominent effect in psychotic pt having
N respiration
• But if he suffers from resp. diseases such
as Asthama them resp. depression

36. • vi) ENDOCRINE EFFECT:
• hyper prolactinemia and inflextility DA,
control prolactin (check its release),if block
hyper prolactinemia manifested by
Gynecomastia in infertility in male and
female
• ix) ANTIEMETIC ACTION:
• Because of DA recep blockade in CRTZ.
Useful in drug induced vomiting and other
vomiting except motion sickness and

37. • x) TEMP. REGULATION:
• Dopaminergic transmission to
hypothalamus is blocked. Temperature
regulation is lost person because
poikelothermic

38. • xiii) SK.MUSCLES:
• in high doses themselves cause
convulsion and spasm
• 2) CVS
• -ve isotropic effects more thioridazine
cause death in young children
• Decrease stroke volume and decrease
CO
• Decrease TPR and alpha adrenergic

40. Adverse effects
1. Neurological side effects
• Parkinsonism
• Acute dystonias
• Neuroleptic malignant syndrome
• Akathisia
• Tardive Dyskinesia
• Perioral tremor (Rabbit syndrome)
2. ANS effects
3. ECG Changes
4. Tolerance & Physical Dependence
5. Reverse Tolerance or super sensitivity.
4. Cholestatic Jaundice

41. 5. Endocrinal effects
6. Hypothermia / Hyperthermia
7. Dermatitis
8. Opacities in lens and cornea
9. Blood Dyscrasias
10. Drug Interactions

42. Therapeutic Uses
A. Treatment of Psychiatric patient
1. Schizophrenia
2. Organic Psychosis
3. Bipolar depression
B. Nausea & vomiting
C. Alcoholic hallucinition
D. Intractable Hiccough

43. • NEUROLEPTIC POISONING:
• Can be homicidal less common suicidal
less chances occure in extreme of
disease.
• Rarely fatal except thio & mesoridazine
duer jto cacdio depressive neuro
musculal, excitability. Convulsions.
• Pt. comatosed.
• Hypothermia, miosis, deep
• Tendon reflexes.
• Tachycacdia
• Thioridazine.

44. • *Monitos vcital fxns.
• * Gastric lavage with activated charcoal
• *Saline catharsis (Na2SO4Mgo)
• * Fluid replacement
• * Pressor agents.
• Diaqzepam for seizerres I/V.
•

45. • PIPERIDINE DERIVATIVE:
• THIORIDAZINE:
– Block D2,x-1 & 5HT-2
– More potent anti muscacinics
• Extrapyramidal (packinsonian) symptoms
duer jto blockade of D2 and balance is
disturbed, in this case balance is notr
distubedf when cholinergicx activity es.
– Sinilac B.A (2s-30%)
– More cacdiotoxic

47. – More macked occulax eff.
• Deposit in retina browning of vision.
• Picture res emble that of retinitis
pigmentosa pt.
• Potency—related to dose.

56. Newer/ Atypical anti-psychotics