antipsycoactive and psycoactive drugs with their classification

1. Presented by
Karanvir Singh
M. PHARMACY
PHARMACEUTICAL CHEMISTRY
PSYCHOACTIVE DRUGS

2. CONTENTS
Psychoactive drugs
Psychosis
Introduction
Psychosis and Schizophrenia
Mechanism Of Action
Classification Of Anti-Psychotic Drugs
Medical Uses
Adverse Effects

3. PSYCHOACTIVE DRUGS

4. PSYCHOSIS
Psychosis (from the Greek , psyche, "mind/soul", and -osis,
"abnormal condition or derangement") refers to an abnormal
condition of the mind.
A syndrome of chronic disordered thinking and disturbed
behaviour (schizophrenia, mania, depression)
The most important types of psychosis are:
Schizophrenia
Affective disorders (e.g. depression, mania)
Organic psychoses (mental disturbances caused by head
injury, alcoholism, or other kinds of organic disease).

5. Schizophrenia
A chronic mental disorder involving a
breakdown in the relation between
thought, emotion, and behaviour, leading
to faulty perception, inappropriate actions
and feelings, withdrawal from reality and
personal relationships into fantasy and
delusion, and a sense of mental
fragmentation.
The disorder is characterized by a
divorcement from reality in the mind of
the person (psychosis).

6. SCHIZOPHRENIA

7. There are four major pathways for the dopamenergic
system in brain :
I. The Nigro-Striatal Pathway.
II. The Mesolimbic Pathway.
III. The Mesocortical Pathway.
IV. The Tuberoinfundibular Pathway.
DOPAMENERGIC SYSTEM

8. SYMPTOMS
OF MESOLIMBIC PATHWAY
POSITIVE SYMPTOMS:
 Delusions
 Hallucinations
 Combativeness
 Insomnia

9. SYMPTOMS OF
MESOCORTICAL PATHWAY
NEGATIVE SYMPTOMS:
 Affective Flattening
(blunt)
 Alogia
 Avolition
 Amotivation
 Apathy
 Asocial Behavior

10. 1. Anxiolytics
Example: benzodiazepines, barbiturates
2. Empathogen–entactogens
Example: MDMA, MDA, 6-APB, AMT
3. Stimulants
This category comprises substances that wake one up, stimulate the
mind, and may cause euphoria, but do not affect perception.
Examples: amphetamine, caffeine, cocaine, nicotine, modafinil
PSYCHOACTIVE DRUGS

11. 4. Depressants ("downers"), including sedatives, hypnotics, and opioids.
This category includes all of the calmative, sleep-inducing, anxiety-
reducing, anesthetizing substances, which sometimes induce perceptual
changes, such as dream images, and also often evoke feelings of
euphoria.
Examples: ethanol (alcoholic
beverages), opioids, cannabis, barbiturates, benzodiazepines.
5. Hallucinogens (Perception without stimulation),
including psychedelics, dissociatives and deliriants. This category
encompasses all those substances that produce distinct alterations in
perception, sensation of space and time, and emotional states
Examples: psilocybin, LSD, Salvia divinorum, nitrous oxide
and scopolamine.

12. 3,4-Methyl​enedioxy​methamphetamine (MDMA)
amphetamine
caffinecocaine

13. Nicotine modafinil
Lysergic acid diethylamide LSD
Hyoscine (scopolamine)

14. ANTI-PSYCHOTIC
DRUGS

15. INTRODUCTION
• Antipsychotics, also known as neuroleptics or major
tranquilizers, are a class of medication primarily used to
manage psychosis (including delusions, hallucinations,
illusion or disordered thought), principally
in schizophrenia and bipolar disorder.
• Antipsychotics are usually effective in relieving symptoms of
psychosis in the short term.
• The long-term use of antipsychotics is associated with side
effects such as involuntary movement disorders, gynecomastia,
and metabolic syndrome. They are also associated with increased
mortality in elderly people with dementia.

18. Mechanism Of Action of First
Generation/Typical Antipsychotic drugs
• Antipsychotic drugs such as haloperidol and chlorpromazine
i.e., first generation Anti-psychotics tend to block dopamine
D2 receptors in the dopaminergic pathways of the brain
• This means that dopamine released in these pathways has less
effect. Excess release of dopamine in the mesolimbic
pathway has been linked to psychotic experiences.
• The excess dopamine release in other pathways, are associated
with psychotic episodes in schizophrenia and bipolar disorder.
Hence, Antipsychotic drugs treat these disorders.

19. – Dopamine receptor–blocking activityin
the brain: All of the first generation
and most of the second- generation
antipsychotic drugs block dopamine
receptors in the brain and the periphery
(exceptclozapine-like atypical).
– The clinical efficacy of the typical
antipsychotic drugs correlates closely
with their relative ability to block D2
receptors in the mesolimbic system of
thebrain.
MECHANISM OF ACTION OF TYPICAL
ANTIPSYCHOTIC DRUGS

20. Classification of First Generation
Anti-Psychotic Drugs
1. PHENOTHIAZINES
1.1 Aliphatic side chain
• Chlorpromazine (CPZ)
• Triflupromazine
Phenothiazine NucleusChlorpromazine Triflupromazine

21. 1.2 PIPERIDINE SIDE CHAIN :
• Thioridazine
• Mesoridazine
ThioridazineMesoridazine
NEWER DRUGS

22. 1.3 PIPERAZINE SIDE CHAIN
• Piperacetazine, Prochlorperazine, Trifluoperazine,Thioethylperazine.
Butaperazine, Perphenazine, Fluphenazine, Acetophenazine, Carphenazine
Prochlorperazine Trifluoperazine Thioethylperazine Piperacetazine
Butaperazine Perphenazine Fluphenazine Acetophenazine

23. Carphenazine

25. 2. BUTYROPHENONES
MOA: Same as phenothiazine
Drugs Available:- Haloperidol, Trifluperidol,
Penfluridol, Droperidol
Haloperidol Trifluperidol Droperidol
Penfluridol
Newer Drugs

26. BUTYROPHENONES SAR
1. X – electron donating group has highest potency
2. Changing the length of the propyl chain decreases potency
3. Replacing the keto oxygen with S, carbon, OH – decreases the
potency
4. Y – replaced with N piperazine structure

27. 3. THIOXANTHENE
• This is a three-ring compound structurally related to
phenothiazine but having the nitrogen atom at position 10
replaced by a carbon atom with a double bond.
• Thioxanthenes have nearly equivalent potency with
phenothiazine
Drugs Chlorprothixene, Flupenthixol, Thiothixene,
Zuclopenthixol, Clopenthixol

28. ThiothixeneFlupenthixolChlorprothixene Clopenthixol
Zuclopenthixol
Newer Drug

30. 4. OTHER HETEROCYCLIC
4.1 Diphenyl butyl piperidines
• Pimozide
4.2 Dibenzoxazepines
• Loxapine
LoxapinePimozide

31. Second Generation/Atypical
Antipsychotics
MOA: Second generation antipsychotics (in particular Atypical
neuroleptics) also antagonize 5-HT2Areceptors.
Different alleles (each of two or more alternative forms of a
gene that arise by mutation and are found at the same place on
a chromosome) of the 5-HT2A receptor have been associated
with schizophrenia and other psychoses, including depression.

32. ATYPICAL ANTIPSYCHOTICS
Mechanism of action
• Most of the second generation agents appear to exert part of
their unique action through inhibition of serotonin receptors
(5-HT2), but they are also a weak dopamine D2 receptor
antagonist

34. CHEMICAL CLASSIFICATION OF
ATYPICALANTIPSYCHOTIC DRUGS
1. Dibenzodiazepine clozapine
2. Thienobenzodiazepine olanzapine
3. Dibenzothiazepine quetiapine
4. Benzisothiazolyl ziprasidone
5. Quinolinone aripiprazole
6. Benzamide sulpride, amisulpride
7. Dibenzethiepine Zotepine
9. Alkylpiperazine Cariprazine

35. DIBENZODIAZEPINE
7 member central ring
moderate potency at DA
α1 and α2 adrenergic 5-
HT2A

36. Resperidone
Olanzpine
QuetiapineZiprasidone
New Drug

37. Sertindole
Aripiprazole
Amisulpride
Sulpride
Cariprazine
Zotepine

38. Cathinone Methcathinone Phthalimidopropiophenone
Mephedrone Methylenedioxypyrovalerone (MDPV)

39. Naphyrone Methylone
Flephedrone Methoxetamine
Phenethylamines
Tryptamine
Cathinone

40. Iloperidone (Fanapt)
• Iloperidone is a monoamine directed towards acting upon and antagonizing specific
neurotransmitters, particularly multiple dopamine and serotonin receptor subtypes. It is
considered an ‘atypical’ antipsychotic because it displays serotonin receptor antagonism,
similar to other atypical antipsychotics. The older typical antipsychotics are primarily
dopamine antagonists.
• Iloperidone has been shown to act as an antagonist at all tested receptors. It exhibits high
affinity to serotonin 5HT2A , dopamine D2 and D3 and noradrenaline α1 receptors,
moderate affinity for dopamine D4, serotonin 5HT6, 5HT7, and low affinity for the
serotonin 5HT1A , dopamine D1 and histamine H1 receptors

41. Paliperidone (Invega)
• Paliperidone is the primary active metabolite of the older antipsychotic risperidone.
While its specific mechanism of action is unknown, it is believed paliperidone and
risperidone act via similar, if not identical, pathways. Its efficacy is believed to result
from central dopaminergic and serotonergic antagonism.

42. Asenapine (Saphris)
Lurasidone (Latuda)

43. Pimavanserin has a unique mechanism of action relative to other antipsychotics,
behaving as a selective inverse agonist of the serotonin 5-HT2A receptor, with 40-
fold selectivity for this site over the 5-HT2C receptor and no
significant affinity or activity at the 5-HT2B receptor or dopamine receptors
PIMAVANSERIN (2016)

44. Brexpiprazole (2018)
Brexpiprazole acts as a partial agonist of the serotonin 5-
HT1A receptor and the dopamine D2 and D3 receptors

45. MEDICAL USES
 Antipsychotics are most frequently used for the following
conditions:
 Schizophrenia: It is a mental disorder characterized
by abnormal behavior and a decreased ability to
understand reality. Common symptoms include false
beliefs, unclear or confused thinking, hearing voices that
others do not, reduced social engagement and emotional
expression, and a lack of motivation.
 Schizoaffective disorder: is a mental disorder characterized
by abnormal thought processes and abnormal emotions.

46.  Bipolar disorder: previously known as manic depression, is
a mental disorder that causes periods of depression and periods
of abnormally elevated mood.
 Psychotic depression: It is a major depressive episode that is
accompanied by psychotic symptoms.
 Dementia: An assessment for an underlying cause of behavior
is needed before prescribing antipsychotic medication for
symptoms of dementia.

47. ADVERSE EFFECTS
 Common adverse effects of antipsychotics include:
• Sedation (particularly common with asenapine, clozapine,
olanzapine, quetiapine, chlorpromazine and zotepine)
• Headaches
• Dizziness
• Diarrhea
• Anxiety
• Extrapyramidal side effects (particularly common with first-
generation antipsychotics), which include:
• Akathisia (an often distressing sense of inner restlessness)
• Dystonia
• Parkinsonism
• Tremor

48. THANKYOU