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Drugs Acting on Central Nervous System 147
2. Second-generation (Atypical) Antipsychotics: Clozapine, Risperidone, Sertindole,
Quetipine, Amisulpride, Aripiprazole, Zotepine.
3. Other Heterocyclics: Pimozide, Loxapine.
5.3.1 Chlorpromazine Hydrochloride
Brand Names: Ormazine, Thorazine, Thorazine Spansule
Chlorpromazine is a phenothiazine that is used to treat psychotic disorders such as
schizophrenia or manic-depression in adults. It is a substituted phenothiazine in which the ring
nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropanamine moiety. The chemical
structure of Chlorpromazine hydrochloride is:
Chemical Name: [3-(2-chloro-10H-phenothiazin-10-yl)propyl]dimethylamine hydrochloride
Properties: Chlorpromazine hydrochloride occurs as odorless white to off-white or creamy white
crystalline powder. It is soluble in methanol, ethanol and chloroform; and practically insoluble in
water, ether and benzene.
Uses: Chlorpromazine is primarily used in the treatment of:
➢ Both acute and chronic psychoses, including schizophrenia.
➢ Bipolar disorder.
➢ Severe behavioral problems in children including those with attention deficit
hyperactivity disorder, nausea and vomiting, anxiety before surgery, etc.
Dosage Forms:
➢ Injectable solution: 25 mg/mL
➢ Oral tablet: 10 mg, 100 mg, 200 mg, 25 mg, 50 mg
Storage and Stability: It decomposes on exposure to air and light. Intact containers should be
stored at controlled room temperature. Freezing should be avoided. Protect the solution from light
during storage or it may discolor. A slightly yellowed solution does not indicate potency loss.
However, a markedly discolored solution should be discarded.
Officials:
➢ Chlorpromazine Hydrochloride, I.P.
➢ Chlorpromazine Hydrochloride Injection, I.P.
➢ Chlorpromazine Hydrochloride Tablet, I.P.
148 Text Book of Pharmaceutical Chemistry
5.3.2 Haloperidol
Brand Names: Haldol, Haldol Decanoate
Haloperidol is a derivative of phenylbutylpiperidine with antipsychotic, neuroleptic, and
antiemetic activities. It consists of a central piperidine structure with hydroxy and p-chlorophenyl
substituents at position 4 and an N-linked p-fluorobutyrophenone moiety.
Chemical Name: 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one
Properties: White to faintly yellowish odorless, amorphous or microcrystalline powder. It is
practically insoluble in water; soluble in approximately 1:60 in alcohol and 1:20 in chloroform;
slightly soluble in ether; and freely soluble in methanol-acetone, benzene and acids.
Uses:
➢ Haloperidol is used in the treatment of certain mental/mood disorders, e.g., schizophrenia.
➢ It is used in mania in bipolar disorder, delirium, agitation, etc.
➢ It can also help to prevent suicide in people who are likely to harm themselves.
➢ It is also used in acute psychosis and hallucinations in alcohol withdrawal.
Storage and Stability: Haloperidol lactate injection should be stored at controlled room
temperature, 25°C to 28°C with and without exposure to light. Exposure to light may cause
discoloration and the development of a greyish-red precipitate over several weeks. Protect oral
dosage forms from light.
Dosage Forms: Haldol (Haloperidol) is available as a sterile parenteral form for intramuscular
injection. The injection provides 5 mg haloperidol (as the lactate) and lactic acid for pH
adjustment between 3.0-3.6.
Officials:
➢ Haloperidol, I.P.
➢ Haloperidol Injection, I.P.
➢ Haloperidol Oral Solution, I.P.
➢ Haloperidol Tablet, I.P.
5.3.3 Risperidone
Brand Names: Risperdal, Risperdal Consta, Perseris, Risperdal M-Tab
Risperidone is a benzisoxazole derivative with antipsychotic property. It acts by decreasing
dopaminergic and serotonergic pathway activity in the brain, therefore decreasing symptoms of
schizophrenia and mood disorders. The structural formula is:
Drugs Acting on Central Nervous System 149
Chemical Name: 3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-
tetrahydropyrido[1,2-a]pyrimidin-4-on
Properties: Risperidone is a white to slightly beige powder. It is practically insoluble in water,
freely soluble in methylene chloride, and soluble in methanol.
Uses: Risperidone is used for the treatment of certain mental/mood disorders such as
schizophrenia, bipolar disorder (manic depression), and irritability associated with autism.
Storage and Stability: Direct contact with heat, air and light may damage your medicines.
Mainly the drug should be kept at room temperature between 68°F and 77°F (20°C and 25°C).
Marketed Preparations:
➢ Risdone MT (Risperidone 0.5 mg tablet) – Intas Pharmaceutical Limited
➢ Risdone Oral Solution (Risperidone 1 mg/mL) – Patriot Pharmaceuticals
➢ Risperidone Tablets 1 mg, 2 mg, 3 mg, 4 mg – Wellona Pharma
➢ Risdone Liquid (Risperidone (1 mg/mL)) – Intas Pharmaceutical Limited
5.3.4 Sulpiride
Sulpiride is a drug of the class benzamides produced by the condensation between the
carboxy group of 2-methoxy-5-sulfamoylbenzoic acid and the primary amino group of (1-
ethylpyrrolidin-2-yl) methylamine.
(R)-(+)-sulpiride is an optically active form of sulpiride having (R)-configuration – the active
enantiomer of the racemic drug sulpiride. It is an enantiomer of a (S)-(-)-sulpiride.
Chemical Name: N-[(1-ethylpyrrolidin-2-yl) methyl]-2-methoxy-5-sulfamoylbenzamide
Uses: Sulpiride is used for the treatment of:
➢ Psychopathological disorders (neurosis, depression and neurotic somatizations)
➢ Treat anxiety and mild depression
150 Text Book of Pharmaceutical Chemistry
➢ Functional psychological disorders
➢ Psychosomatic syndromes
➢ Senile dementia
➢ Gastrointestinal somatizations, Vertigo, etc.
Storage and Stability: Store in cool and dry place, below at 25°C. Store in the original package
in order to protect from light.
Marketed Preparations:
➢ Dogmatil, Sulpiride Dogmatil 200 mg Tablets) – Sanofi Aventis
➢ Livosulpiride Injection – India mart
➢ Sulpiride 200 mg (Sulpiride 200 mg Tablets) – Saintroy Lifescience
➢ Sulpiride Capsules 50 mg (Sulpir Care™) – Adva Care
5.3.5 Olanzapine
Brand Names: Lybalvi, Olazax, Symbyax, Zalasta, Zypadhera, Zyprexa
Olanzapine belongs to the thienobenzodiazepine class. It is 10H-thieno[2,3-b][1,5]
benzodiazepine substituted by a methyl group at position 2 and a 4-methylpiperazin-1-yl group at
position 4. The chemical structure is:
Chemical Name: 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2, 3-b][1, 5]benzodiazepine
It binds with the following receptors: serotoninergic, dopaminergic, muscarinic M1-5, histamine
H1, and alpha-1-adrenergic receptors and binds weakly with gamma-aminobutyric acid type
A, benzodiazepine, and beta-adrenergic receptors. It provides anti-nausea and anti-emetic effects
due to the blockade of 5-HT2 and 5-HT3 receptors for serotonin.
Properties: It occurs as a yellow crystalline solid, which is practically insoluble in water.
Uses:
➢ Olanzapine is used for the treatment of Schizophrenia.
➢ It is used in cute mania in bipolar disorder.
➢ It is used in agitation associated with schizophrenia and bipolar disorder.
➢ It has also been established in treating depression off-label because of its mood-
stabilizing properties.
Drugs Acting on Central Nervous System 151
Dose and Strength: It is available as a pill that comes in the strengths of 2.5 mg, 5 mg, 7.5 mg,
10 mg, 15 mg and 20 mg, and as Zydis orally disintegrating tablets in the strengths of 5 mg,
10 mg, 15 mg and 20 mg.
Marketed Preparations:
➢ Olanzapine 10 mg, Mouth Dissolving Tablets – Intas Pharmaceutical Limited
➢ Olanzapine Tablets USP 5 mg – Taj Pharma
➢ Molanza 7.5 Olanzapine Mouth Dissolving Tablets
5.3.6 Quetiapine
Brand Names: Seroquel, Seroquel XR
Quetiapine is a tetracyclic compound and is a dibenzothiazepine derivative, with an
N-alkylpiperazine and a N-arylpiperazine having atypical antipsychotic property. Atypical
antipsychotics (AAP) are also known as second generation antipsychotics (SGAs) and serotonin-
dopamine antagonists (SDAs). The structural formula is:
Chemical Name: 2-[2-(4-dibenzo [b,f][1,4]thiazepin-11-ylpiperazin-1-yl)ethoxy]ethanol
Properties: Quetiapine occurs as a white to off-white crystalline powder which is moderately
soluble in water.
Uses:
➢ Quetiapine is primarily used as an antipsychotic drug (also known as major tranquilizers
and neuroleptics).
➢ It is used for the treatment of schizophrenia.
➢ It is used for the treatment of bipolar disorder and major depressive disorder.
➢ It is widely used as a sleep aid due to its sedating effect.
➢ It is used for the treatment of moderate to severe manic episodes in bipolar disorder.
➢ They are also frequently used to treat agitation associated with dementia, anxiety
disorder, autism spectrum disorder, and obsessive-compulsive disorder (an off-label use).
Storage and Stability: Quetiapine should be stored at room temperature and refrigerated
temperature (4°C) for 60 days. Quetiapine Oral Suspension should be stored in a refrigerator (2-
8ºC in the original package (bottle) in order to protect from light.
152 Text Book of Pharmaceutical Chemistry
Dose and Strength: Quetiapine (Brand: Seroquel) available in immediate-release oral tablet with
strengths: 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, and 400 mg.
Marketed Preparations:
➢ Quetiapine Tablets 25 mg – Taj Pharma
➢ Quetiapine Oral Suspension – Rosemont Pharma
➢ Queviz-100 (Quetiapine Tablets I.P.) – Tanishq Life Care
➢ Seroquin-100 (Quetiapine Fumarate) – Cipla Limited
➢ Moquet-100 (Quetiapine Fumarate Tablets I.P.) – Intas Pharmaceuticals Ltd.
5.3.7 Lurasidone
Brand Name: Latuda
Lurasidone is an N-arylpiperazine, a second generation (atypical) antipsychotic agent. It is
generally used as the hydrochloride salt for the treatment of schizophrenia. The chemical structure
is:
Chemical Name: (1R,2S,6R,7S)-4-[[(1R,2R)-2-[[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]methyl]
cyclohexyl]methyl]-4-azatricyclo[5.2.1.0
2,6
]decane-3,5-dione
Properties: Lurasidone hydrochloride occurs as a white to off-white powder. It is very slightly
soluble in water, practically insoluble or insoluble in 0.1 N HCl, slightly soluble in ethanol,
sparingly soluble in methanol, practically insoluble or insoluble in toluene, and very slightly
soluble in acetone.
Uses: Lurasidone is used in the treatment of:
➢ Schizophrenia in adults and adolescents
➢ Depressive episodes associated with bipolar I disorder in adults and pediatric patient
➢ Effective in improving mood with bipolar I disorder in adults as adjunctive therapy
with lithium or valproate
Dosage Forms: Oral tablet (120 mg, 20 mg, 40 mg, 60 mg, 80 mg)
Marketed Preparations:
➢ Luramax 40 mg Tablet – Sun Pharmaceutical Industries Limited
➢ Tablura 40 mg Tablet – Cipla Limited
➢ Lurafic 40 mg Tablet – Lupin Limited
Drugs Acting on Central Nervous System 153
5.4 ANTICONVULSANTS
Convulsion is defined as a sudden, violent, and irregular movement of the body, caused by
involuntary muscle contraction and spasm in the brain’s nerve cells. It can be caused due to
number of medical conditions, including epilepsy, trauma, severe fever, an inflammatory brain
infection, exposure to toxins and by certain medications. Sometimes, the word convulsion uses
interchangeably with seizures, although seizures refers to an electrical disturbance in the brain.
Types of Convulsions
There are many types of seizures. The type of seizure depends on where it begins in the brain
and how far it spreads. The majority of seizures last from 30 seconds to 2 minutes. A seizure
lasting more than five minutes is considered a medical emergency. Epileptic seizures may be
categorized in:
1. Focal or partial seizures: These seizures occur when seizure activity is limited to a
part of one brain hemisphere. There is a site, or a focus, in the brain where the seizure
begins. There are two types of focal seizures: (i) Focal-aware seizures and (ii) Focal-
impaired awareness seizures.
2. Generalized tonic-clonic seizures: These seizures are also known as grand mal
seizures. They occur when there is widespread seizure activity in the left and right
hemispheres of the brain. The different types of generalized seizures are:
➢ Myoclonic seizures: Characterized by sporadic and brief jerking, typically on both
sides of the body.
➢ Absence seizures (formerly known as petit mal).
➢ Tonic-clonic or convulsive seizures (formerly known as grand mal).
➢ Atonic seizures: Start with a myoclonic disease before muscle control is abruptly
lost.
➢ Clonic seizures: Only involve jerking and spasms.
➢ Tonic seizures: Only involve stiffening.
Chemical Classification of Anticonvulsant Drugs: Based upon the chemical structures,
antiepileptic drugs are classified into following classes:
Barbiturate : Phenobaritone
Deoxybarbiturate : Primidone
Hydantoin : Phenytoin
Iminostillbene : Carbama zepine
Succinimide : Ethosuximide
Aliphatic Carboxylic Acid : Valproic acid
Benzodiazepines : Clonazepam, Diazepam
Phenyltriazine : Lamotrigine
Cyclic GABA Analogue : Gabapentine
Newer Drugs : Vigabatrine, Zonisamide
154 Text Book of Pharmaceutical Chemistry
5.4.1 Phenytoin
Brand Names: Dilantin, Phenytek
Phenytoin belongs to the class of organic compounds known as phenylhydantoins. These are
heterocyclic aromatic compounds containing an imiazolidinedione moiety substituted by a phenyl
group. It works by reducing the spread of seizure activity in the brain. Phenytoin has the
following structural formula:
Chemical Name: 5,5-Diphenyl-imidazolidine-2,4-dione
Properties: Phenytoin appears as fine white or almost white odorless, tasteless, crystalline
powder. It is practically insoluble in water; slightly soluble in chloroform and ether; soluble in
alcohols; and freely soluble in warm propylene glycol. Its melting point is 295-298°C. Phenytoin
sodium is slightly hygroscopic. On exposure to air, it gradually absorbs carbon dioxide with the
liberation of phenytoin.
Uses: Phenytoin is an anticonvulsant medication that is used in a wide variety of seizures. It is
also used as an anti-arrhythmic and a muscle relaxant agent.
➢ Phenytoin is used in tonic-clonic seizures (grand mal).
➢ It is used in simple or complex partial (psychomotor or temporal lobe) seizures.
➢ It is indicated for the control of tonic-clonic seizures (grand mal).
➢ It is used for the treatment of focal seizures.
➢ It is used in absence seizures.
➢ It is indicated for the control status epileptics.
➢ It is used in abnormal heart rhythms (ventricular tachycardia and atrial tachycardia).
Dosages of Phenytoin: Phenytoin is available under the following different dosages:
➢ Capsule (30 mg, 100 mg, 200 mg and 300 mg)
➢ Tablet, chewable (50 mg)
➢ Oral suspension (125 mg/5 mL)
➢ Injectable solution (50 mg/mL)
Drugs Acting on Central Nervous System 155
Storage and Stability: Store the medicine in a closed container at room temperature, away from
heat, moisture and direct light. Keep from freezing. Store at 20°C to 25°C (68°F to 77°F). Shelf-
life of the substance 5 years is 20°C.
Marketed Preparations:
➢ Dilantin (Phenytoin) 25 mg, 50 mg and 100 mg – Pfizer
➢ Epsolin 50 mg – Zydus Neurosciences
➢ Fentoiner 100 mg – Sun Pharmaceuticals Industries Limited
5.4.2 Carbamazepine
Brand Names: Carbatrol, Carnexiv, Epitol, Equetro, Tegretol, Carbamazepine Chewtabs,
Carbamazepine CR, Teril
Carbamazepine is a tricyclic compound consist of dibenzoazepine that is 5H-dibenzo [b,f]
azepine carrying a carbamoyl substituent at the azepine nitrogen. Its structural formula is:
Chemical Name: 5H-dibenzo[b,f]azepine-5-carboxamide
Properties: It occurs as white to yellowish-white crystal, almost odorless. Carbamazepine can
either have no taste or be slightly bitter. It is practically insoluble in water and ether but soluble in
acetone, alcohol, carbon tetrachloride, chloroform, dimethylformamide dioxane and propylene
glycol. Melting point is 190°C to 193°C.
Uses: Carbamazepine has both antiepileptic and psychotropic properties.
➢ It is widely used in therapy of epilepsy.
➢ It is used as an anticonvulsant for the treatment of generalized tonic-clonic (grand mal)
and psychomotor or partial (focal) seizures.
➢ It may also be used in the management of bipolar disorder, and has analgesic properties.
➢ It is used in Pain syndromes: Trigeminal neuralgia and glossopharyngeal neuralgia.
➢ It is used as an adjunctive treatment in schizophrenia along with other medications and as
a second-line agent in bipolar disorder.
Storage and Stability: Store in airtight containers, below 40°C and, preferably, between 15°C
and 30°C, and away from light.
Dosage Forms:
➢ Chewable tablet (Epitol): 100 mg
➢ Tablet, extended-release (Tegretol XR): 100 mg, 200 mg and 300 mg
➢ Capsule, extended-release (Equetro, Carbatrol): 100 mg, 200 mg and 300 mg
➢ Oral suspension (Teril): 100 mg/5 ml
156 Text Book of Pharmaceutical Chemistry
Marketed Preparations:
➢ Carbatol CR 200 mg Tab – Torrent Pharma
➢ Tegrital 200 mg Tablet – Novartis India
➢ Mazetol 200 mg Tablet 10s – Abbott India
5.4.3 Clonazepam
Brand Names: Clonapam, Klonopin, Rivotril
Clonazepam is a benzodiazepine derivative. It is an anticonvulsant drug used in myotonic or
atonic seizures, absence seizures, and photosensitive epilepsy.
IUPAC Name: 5-(2-chlorophenyl)-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one
Properties: It occurs as off-white to light yellow crystalline powder. Its melting point is 238°C-
240°C. It is practically insoluble in water, slightly soluble in alcohol and in methyl alcohol,
sparingly soluble in acetone and in chloroform, and very slightly soluble in ether.
Uses:
➢ Clonazepam is used to prevent and treat all types of epilepsy and seizures, panic
disorder, anxiety, and the movement disorder known as akathisia.
➢ Drug is also used as a treatment for panic attacks, insomnia, and symptoms related
to chronic anxiety and anxiety disorders.
➢ It works by calming your brain and nerves.
➢ It is also used myoclonus and associated abnormal movements, and panic disorders.
Dosage Forms: Tablet dispersible: 0.12 mg, 0.25 mg, 0.5 mg, 1 mg, 2 mg
Official:
➢ Clonazepam Injection I.P.
5.4.4 Valproic Acid
Brand Names: Depakene, Valproate Sodium, Depacon, Stavzor Depakote, Epival
Valproic acid is synthetic derivative of branched-chain saturated fatty acid which consists of
a propyl substituent on a pentanoic acid stem. It derives from a valeric acid and a conjugate acid
of a valproate.