Antipsychotics

Antipsychotics are a group of psychotropic drugs used to treat psychosis by primarily blocking dopamine (D₂) receptors and/or serotonin (5-HT₂) receptors in the brain.

                                                            OR

“Antipsychotics, also called neuroleptics, are a class of psychotropic agents that act mainly through dopamine D₂ receptor antagonism (typical antipsychotics) or combined dopamine and serotonin (5-HT₂A) receptor antagonism/partial agonism (atypical antipsychotics)."

Example-  Used in the treatment of schizophrenia, bipolar disorder, drug-induced psychosis, hallucinations, delusions, agitation, or thought disorders.

Drugs Classification With MOA

I. First Generation Antipsychotics (Strong D₂ blockade to ↓ Positive symptoms, but ↑ EPS & prolactin)

1. High Potency

• Haloperidol
• Fluphenazine
• Trifluoperazine
• Pimozide

2. Low Potency

• Chlorpromazine
• Thioridazine

II. Second Generation (Atypical) Antipsychotics (D₂ blockade (weak) + 5-HT₂A blockade to ↓ Positive + Negative symptoms, less EPS, but metabolic side effects)

• Clozapine (unique: effective in treatment-resistant schizophrenia, ↓ suicide risk)
• Risperidone
• Olanzapine
• Sulpiride
• Quetiapine
• Ziprasidone
• Lurasidone
• Aripiprazole (partial D₂ agonist)

III. Third Generation Antipsychotics (D₂ partial agonist + 5-HT₂A blockade to Balanced dopamine effect, mood stabilization, minimal EPS)

• Aripiprazole
• Brexpiprazole
• Cariprazine

NOTE:

• “Blockade” means blocking or preventing the action of a receptor by a drug.

                                                                    OR

Blockade = receptor antagonism = preventing the neurotransmitter from acting at its receptor.

• EPS = Extrapyramidal Symptoms (drug-induced movement disorders that occur mainly due to dopamine (D₂) receptor blockade in the nigrostriatal pathway of the brain).

Fig. 01

                                                                        -:Chlorpromazine:- 

 Chemical Name

Generic name: Chlorpromazine Hydrochloride
IUPAC name: 2-chloro-10-(3-dimethylaminopropyl)phenothiazine hydrochloride

Molecular formula: C17​H19​ClN2​S⋅HCl

Molecular weight: 355.33 g/mol

Chemical structure 

• Phenothiazine ring system (tricyclic system with sulfur and nitrogen in the central ring).
• A chlorine atom is attached at the 2-position of the phenothiazine ring.
• At the 10-position nitrogen, a 3-dimethylaminopropyl side chain is attached.

 Stability Condition

• Sensitive to light → decomposes on prolonged light exposure (solution may discolor).
• Stable at room temperature, but prolonged exposure to air/moisture may cause degradation.
• Avoid alkaline pH.

Storage Condition

• Store in a tightly closed container, protected from light and moisture.
• Temperature: 20–25 °C (controlled room temperature).
• Injection forms should be stored below 25 °C and protected from freezing.

Types of formulations

• Tablets 
• Capsules
• Oral solution / Syrup
• Injection
• Suppositories 

 Brand Names

• Thorazine 
• Largactil
• Chlorprom
• Megaphen 
• Hibernal 

Uses

Chlorpromazine is a typical antipsychotic (first-generation neuroleptic).

Psychiatric uses:

• Schizophrenia
• Acute psychosis, mania
• Severe anxiety (short-term)

Other medical uses:

• Control of nausea & vomiting (antiemetic, especially in chemotherapy or palliative care)
• Intractable hiccups
• Preoperative sedation
• Management of acute intermittent porphyria
• Adjunct in tetanus

                                                          -:Haloperidol:-

Chemical Name

4-[4-(p-chlorophenyl)-4-hydroxypiperidino]-4’-fluorobutyrophenone

Chemical Structure

• Belongs to Butyrophenone derivatives.
• Contains a butyrophenone backbone with a piperidine ring, fluorophenyl group, and chlorophenyl group.

 Stability Condition

• Stable under normal conditions of use.
• Sensitive to light and air → may degrade with prolonged exposure.
• Avoid extreme temperatures.

Storage Conditions

• Store at controlled room temperature (20–25 °C).
• Protect from light and moisture.
• Keep in tightly closed container.
• Injectable form should not be frozen.

Types of Formulations

• Tablets 
• Oral liquid (drops/solution)
• Rectal suppositories
• Injection

 Brand Names

• Haldol 
• Serenace
• Halopid
• Dozic 

 Uses (Therapeutic Applications)

Haloperidol is a typical antipsychotic (butyrophenone derivative).
Main indications:

• Schizophrenia (positive symptoms like hallucinations, delusions)
• Acute psychosis
• Mania (bipolar disorder)
• Delirium (short-term management)
• Tourette’s syndrome (tics, vocal utterances)
• Severe agitation and aggression
• Nausea & vomiting (antiemetic use in some cases)
• Huntington’s chorea (to control hyperkinesia)

                                                            -:Risperidone:- 

Chemical Name

IUPAC Name:
3-[2-[4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one
Molecular Formula: C₂₃H₂₇FN₄O₂
Molecular Weight: 410.49 g/mol

Chemical Structure

Stability Condition

Risperidone is stable under normal conditions but:

• Sensitive to light (photodegradation may occur).
• Stable in the solid form at room temperature.
• In aqueous solution: more stable at slightly acidic pH (around 4–6).
• Degrades faster under alkaline conditions and high temperature.

Storage Condition

• Store at 20–25 °C (room temperature).
• Protect from light and moisture.
• Keep tablets in tightly closed container.
• For oral solution: refrigerate after opening, use within the recommended period (usually 2 months).

Types of formulations

• Tablets
• Orally Disintegrating Tablets (ODT)
• Solution / Syrup
• Injection
• Sublingual

Brand Names

• Risperdal 
• Rispidon
• Risnia
• Risperdal Consta 

Uses

• Schizophrenia
• Bipolar disorder 
• Irritability associated with autism
• Aggression and behavioral disorders 

                                                                                   -:Sulpiride:-

Chemical Name

IUPAC: N-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxy-5-sulfamoylbenzamide
Formula: C15H23N3O4S
Molecular Weight: 341.43 g/mol

Chemical Structure

Sulpiride belongs to the substituted benzamide class.

• Benzamide backbone
• Methoxy group at position 2
• Sulfonamide group at position 5
• Side chain: ethylpyrrolidylmethyl substituent

Stability Conditions

• Stable under normal storage conditions.
• Sensitive to light and moisture.
• Decomposes on prolonged exposure to heat.

Storage Conditions

• Store at room temperature (15–30 °C).
• Keep in tight, light-resistant containers.
• Protect from moisture and direct sunlight.

Types of formulation

• Tablets 
• Capsules
• Oral suspension 
• Injectable solution 

Brand Names

• Dogmatil (Sanofi)
• Dolmatil
• Sulpitac
• Eglonyl

Uses 

• Antipsychotic (atypical) – selective dopamine D₂ receptor antagonist.
• Schizophrenia (positive & negative symptoms, esp. negative).
• Depression with psychotic features.
• Vertigo & vestibular disorders.
• Dysthymia, anxiety states (off-label in some countries).
• Peptic ulcer / functional dyspepsia (older use due to prokinetic effects)

                                                       -:Olanzapine:-

Chemical Name

• IUPAC Name: 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine

Chemical Structure

• Belongs to the thienobenzodiazepine class.
• Contains a benzodiazepine ring fused with a thiophene ring and substituted piperazine group.

Stability Condition

• Stable under recommended storage conditions.
• Sensitive to light, moisture, and high temperature.
• Degrades if exposed to strong oxidizing agents

Storage Condition

• Store at 25°C (77°F); excursions permitted between 15–30°C.
• Protect from light and moisture.
• Keep in tight, closed containers.
• Injectable forms: should not be frozen.

Types of Formulation

• Tablets 
• Orally Disintegrating Tablets (ODT) 
• Intramuscular Injection 

Brand Names

• Zyprexa
• Zydis (ODT form)

Uses

• Schizophrenia
• Bipolar disorder 
• Depression (resistant cases) 

                                                                                  -:Quetiapine:-

Generic Name: Quetiapine
IUPAC Name (chemical name):
2-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]ethanol
Molecular Formula: C₂₁H₂₅N₃O₂S
Molecular Weight: ~383.5 g/mol

Chemical Structure

• A di-benzothiazepine ring system (tricyclic nucleus)
• A piperazine ring substitution
• An ethanol side chain

Stability Condition

• Stable under normal storage conditions.
• Sensitive to excessive heat and moisture.
• Light exposure should be minimized.
• Hydrolysis and oxidation may occur if improperly stored.

 Storage Condition

• Store at 20–25 °C (room temperature).
• Protect from light and moisture.
• Keep in a tightly closed container.
• Do not freeze liquid formulations.

Types of Formulations

• Immediate-release (IR) tablets
• Extended-release (XR) tablets 
• Oral suspension 
• Injectable forms 

 Brand Names

• Seroquel 
• Seroquel XR
• Qutipin
• Ketipinor
• Quetapel 

 Uses

• Schizophrenia 
• Bipolar disorder
• Major depressive disorder (MDD) 
• Generalized anxiety disorder 
• Insomnia

                                                                              -:Lurasidone:-

Chemical Name 

Chemical Structure

Belongs to the atypical (second-generation) antipsychotics.

Contains:

• A benzisothiazole ring
• A piperazine ring
• A cyclohexylmethyl group
• A phthalimide moiety

Stability Condition

• Stable under normal temperature and humidity.
• Sensitive to light 
• Stable between 15–30 °C, but avoid high heat.

Storage Condition

• Store at room temperature (20–25 °C).
• Protect from light and moisture.
• Keep in airtight containers.
• Avoid freezing.

Types of Formulation

Tablet

Brand Name

 Latuda®

Uses 

• Schizophrenia (adults and adolescents).
• Bipolar depression
• In major depressive disorder (MDD).