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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5265_Библиотеки_им_академика_М_И_Перельмана.pdf
Drugs Acting on Central Nervous System 157
Chemical Name: 2-propylpentanoic acid
Properties: Valproic acid is a clear colorless to pale yellow, liquid-viscous liquid. It is slightly
soluble in water (1.2 mg/mL); and fully soluble in acetone, chloroform, ether and methyl alcohol.
Uses:
➢ Valproic acid is used for the treatment of different types of seizure disorders.
➢ It is used as an anticonvulsant for the treatment of absence seizures, partial seizures,
and generalized seizures.
➢ It is also used to treat manic episodes related to bipolar disorder (manic depression).
➢ It is used to prevent migraine headaches.
Storage Conditions: Store in airtight containers and protect from light. Valproic acid capsules
should be stored at 15°C to 30°C and freezing should be avoided.
Dosage Forms:
➢ Intravenous solution (100 mg/mL)
➢ Oral capsule (250 mg)
➢ Oral liquid (250 mg/5 ml)
Marketed Preparations:
➢ Divuna-ER 250 mg – Dr. Reddy’s Laboratories Limited
➢ Convulex 500 mg ER (Valproic acid 500 mg Tablet) – A.N. Pharmacia
➢ Depakote Syrup (Valproic Acid 250 mg/5 ml Syrup) – Abbott Healthcare Pvt. Ltd.
➢ Encorate 100 mg Injection (Sodium Valproate 100 mg Injection) – Sun Pharmaceuticals
Industries Limited
5.4.5 Gabapentin
Brand Names: Neurontin, Gralise, Gabarone, Fanatrex
Gabapentin is a structural analog of gamma-amino acid. It is a 3,3-disubstituted derivative of
GABA. The structure of gabapentin is formed by the addition of a cyclohexyl group to GABA.
Cyclohexane ring is substituted at position 1 by aminomethyl and carboxymethyl groups. The
structural formula of gabapentin is:
158 Text Book of Pharmaceutical Chemistry
Properties: Gabapentin is a white to off-white crystalline solid. It is freely soluble in water and
both basic and acidic aqueous solutions.
Uses:
➢ Gabapentin is used to treat partial seizures.
➢ It is used for the treatment of neuropathic pain caused by diabetic neuropathy, post-
herpetic neuralgia and central pain.
➢ It is used in anxiety and bipolar disorders.
➢ It is also used in the prevention of episodes of migraine.
➢ It is used to treat and prevent hot flashes (sudden strong feelings of heat and sweating) in
women who are being treated for breast cancer or in menopause.
Dosage Forms: Gabapentin comes as a capsule, a tablet, an extended-release (long-acting) tablet,
and an oral solution (liquid).
➢ Gabapentin Capsules – 100 mg, 300 mg and 400 mg
➢ Neurontin (Gabapentin) Tablets – 300 mg, 600 mg and 800 mg
➢ Neurontin (Gabapentin 50 mg/5 ml) 2 m L4 (70 ml)
Marketed Preparations:
➢ Gabapentin Tablets 400 mg – Wellona Pharma Pvt. Ltd.
➢ Gabator 300 (Gabapentin I.P. 300 mg capsule)
5.4.6 Topiramate
Brand Names: Eprontia, Qsymia, Qudexy, Topamax, Trokendi
Topiramate is a sulfamate-substituted monosaccharide derived from fructose with
anticonvulsant property. It is most frequently prescribed for the prevention of migraines as it
decreases the frequency of attacks. The structural formula of Topiramate is:
Chemical Name: 2,3,4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
Properties: Topiramate occurs as a white crystalline powder with a bitter taste. It is most soluble
in alkaline solutions containing sodium hydroxide or sodium phosphate. It is freely soluble in
acetone, chloroform, dimethylsulfoxide and ethanol.
Drugs Acting on Central Nervous System 159
Uses:
➢ Topiramate is used to treat symptoms of certain types of seizures in adults.
➢ It is used to treat migraine headaches.
➢ It is used in epilepsy for treatment of generalized or focal seizures.
➢ It is used to treat Lennox-Gastaut Syndrome (LGS) (a complex, rare and severe
childhood-onset epilepsy).
➢ It has been used as a treatment for alcoholism.
➢ It is used for the treatment of obesity.
Dosage Forms:
Topiramate comes as a:
➢ Oral capsule: 15 mg and 25 mg
➢ Oral capsule extended release: 100 mg, 150 mg, 200 mg, 25 mg and 50 mg
➢ Oral tablet: 100 mg, 200 mg, 25 mg and 50 mg
Storage: Store the drug in a tightly closed container at controlled room temperature away from
light and moisture.
Marketed Preparations:
➢ Topaz-100 (Topiramate Tablet I.P. 100 mg) – Intaz
➢ Topilep (Topiramate Tablet I.P. 50 mg) – Aripolis Biotech Pvt. Ltd.
➢ Topamac (Topiramate Tablet I.P. 25 mg) – Janseen Pharmaceutical Pvt. Ltd.
➢ Top AMAXX (Topiramate Capsules) – Janssen Pharmaceuticals Inc.
5.4.7 Vigabatrin
Brand Names: Sabril, Vigadrone
Vigabatrin is a structural analogue of GABA having a gamma-vinyl GABA structure. It is
also known as γ-vinyl-GABA. The structural formula of Vigabatrin is:
Chemical Name: 4-aminohex-5-enoic acid
Properties: Vigabatrin occurs as a white to off-white granular powder. It is freely soluble in
water and in aqueous solvents, slightly soluble in methanol, very slightly in ethanol and
chloroform, and practically insoluble in toluene and n-hexane.
160 Text Book of Pharmaceutical Chemistry
Uses:
➢ Vigabatrin is used to treat infantile spasms (spasms in babies and children between the
ages of 1 month and 2 years).
➢ It is also used to treat seizures in succinic semialdehyde dehydrogenase deficiency
(SSADHD).
➢ It is used in combination with other medications to treat seizure disorders (epilepsy).
➢ It is used in Focal Impaired Awareness or Complex Partial Seizures.
➢ It is used in Temporal Lobe Epilepsy.
➢ It is used in Secondarily Generalized Seizures or Bilateral Tonic Clonic Seizures.
Dosage Forms: Vigabatrin comes as:
➢ Oral powder for reconstitution: 500 mg
➢ Oral tablet: 500 mg
Storage: Sabril should be stored at room temperature, away from light and moisture.
Marketed Preparations:
➢ Vigatridin 500 mg (Vigatridin 500 mg Tablet) – Biozenta Lifescience
➢ Sabril 500 mg (Vigatridin 500 mg Tablet) – Sanofi Aventis
➢ Vigabatrin Oral Solution, USP 500 mg/packet – Teva
5.4.8 Lamotrigine
Brand Name: Lamictal
Lamotrigine is a 1,2,4-triazine derivative; triazene ring is substituted by amino groups at
positions 3 and 5, and by a 2,3-dichlorophenyl group at position 6. It is used as a first line drug
for the treatment of generalized tonic-clonic seizures. The structural formula of Lamotrigine is:
Chemical Name: 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine
Uses:
➢ Lamotrigine is used to treat mood swings of bipolar disorder (manic depression) in adults.
➢ It is used to treat the partial seizures such as primary generalized tonic-clonic seizures and
bipolar I disorder maintenance.
➢ It is used to treat Lennox-Gastaut syndrome.
Drugs Acting on Central Nervous System 161
➢ It is used to treat schizophrenia,
➢ It is used to treat unipolar depression.
➢ It is used as an antidepressant, a non-narcotic analgesic.
➢ It is used to reduce neuropathic pain.
Properties: It occurs as a white to pale cream-colored powder crystals from isopropanol.
It is very slightly soluble in water and slightly soluble in 0.1 M HCl.
Dosage Forms: Lamotrigine is available in formulations of 25 mg, 100 mg, 150 mg and 200 mg
tablets in a tablet form. A chewable and dispersible tablet available in 2 mg, 5 mg, and 25 mg
respectively.
Storage: It should be stored at room temperature, away from light and moisture. Keep the
container tightly closed and Don't store these drugs in moist or damp areas, such as bathrooms.
Marketed Preparations:
➢ Lamight 50 (Lamotrigine 50 mg Tablets) – Psychocare Health Pvt. Ltd.
➢ Lamogine (Lamogine 25 mg Tablet I.P.) – DD Pharmaceuticals
➢ Lamitor OD 100 (Lamotrigine 100 mg Tablets) – Torrent Pharmaceuticals Limited
5.5 ANTI-DEPRESSANTS
Depression is a mood disorder that involves a persistent feeling of sadness and loss of
interest. It is also known as major depressive disorder. It is an illness that may occur with other
mental disorders and other illnesses such as diabetes, cancer, heart disease and chronic pain.
Common forms of depression are:
➢ Major depression: Depression most of the time for at least 2 weeks that affect the ability
to work, sleep, study and eat.
➢ Persistent depressive disorder: It includes less severe symptoms of depression and lasts
for at least 2 years.
➢ Perinatal depression: It occurs in a woman during pregnancy or after delivery
(postpartum depression).
➢ Seasonal affective disorder: It typically starts in late fall and early winter and going
away during spring and summer.
➢ Depression with symptoms of psychosis: It is a severe form of depression where a
person experiences psychosis symptoms, e.g., delusions or hallucinations.
Anti-depressants are class of medications that can reduce symptoms of depression, social
anxiety disorder, anxiety disorders, seasonal affective disorder, and dysthymia, or mild chronic
depression, as well as other conditions. Anti-depressants drugs relieve these symptoms by
correcting chemical imbalances of neurotransmitters in the brain. Chemical imbalances may be
responsible for changes in mood and behavior.
162 Text Book of Pharmaceutical Chemistry
Classification of Anti-depressants
There are mainly 5 classes of anti-depressants drugs that are commonly used to treat
depression.
1. Selective serotonine reuptake inhibitors: Fluoxetine, Fluvoxamine, Paroxetine,
Sertraline, Citalopram and Escitalopram.
2. Atypical anti-depressants: Trazodone, Mianserin, Mirtazapine, Venlafaxine,
Duloxetine, Tianeptine, Amineptine and Bupropion.
3. Tricyclic anti-depressants:
➢ NA + 5HT reuptake inhibitors: Imipramine, Amitriptyline, Trimipramine,
Doxepin, Dothiepin and Clomipramine.
➢ Predominantly NA reuptake inhibitors: Nortriptyline, Amoxapine, Reboxetine
and Desipramine.
4. Monoamine oxidase inhibitors (MAOI): Phenelzine, Tranylcypromine and
Moclobemide.
5. Drug used to treat mania and bipolar disorder: Carbamazepine, Lithium salt and
Valproic acid.
5.5.1 Amitriptyline Hydrochloride
Brand Names: Elavil, EnovaRX, Equipto Amitriptyline, Vanatrip
Amitriptyline hydrochloride is an organic tricyclic compound, also known as Elavil. It is the
hydrochloride salt of the tricyclic dibenzocycloheptadiene amitriptyline. The structural formula of
Amitriptyline hydrochloride is:
Properties: It occurs as a white, odorless, crystalline powder or small crystals. It is freely soluble
in water, alcohol, chloroform and methanol; and insoluble in ether.
Uses: Amitriptyline hydrochloride is used for:
➢ Treatment of major depressive disorder.
➢ Treatment of Neuropathic pain.
➢ Treatment of Fibromyalgia.
➢ Prophylactic treatment of migraine in adults.
➢ Treatment of Nocturnal enuresis in children.
➢ Prophylactic treatment of chronic tension type headache (CTTH) in adults.
Drugs Acting on Central Nervous System 163
Dosage Form: Amitriptyline hydrochloride is available in Oral Tablets: 10 mg, 25 mg, 50 mg, 75
mg, 100 mg and 150 mg.
Storage: Store the medicine in a closed container at room temperature, away from heat, moisture
and direct light. Keep away from freezing. Store between 68°F to 77°F; excursions permitted
59°F to 86°F.
Marketed Preparations:
➢ Triptbeta-25 (Amitriptyline hydrochloride Tablet I.P) – Betamax
➢ PSYCOMER-10 (Amitriptyline Hydrochloride 10) – Psycogen
➢ Arrow-Amitriptyline (Amitriptyline Hydrochloride) –Actavis
5.5.2 Imipramine Hydrochloride
Brand Names: Tofranil, Tofranil-PM
Imipramine Hydrochloride is a synthetic tricyclic derivative. It is a hydrochloride salt form
of imipramine that is widely used in the therapy of depression. The structural formula of
Imipramine Hydrochloride is:
Chemical Name: 3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethylpropan-1-amine;
hydrochloride
Properties: Imipramine Hydrochloride occurs as a white to off-white, odorless, or practically
odorless, crystalline powder with a burning taste. It is freely soluble in water and ethanol; and
practically insoluble in ether and in benzene. Melting point is 170°C -174°C.
Uses:
➢ Imipramine hydrochloride is effective in depressive syndromes, particularly those
associated with manic-depressive and involutional psychoses. (A mental disturbance
occurs during menopause or later life.)
➢ It is effective in treating anxiety and panic disorder.
➢ It is used to treat nocturnal enuresis (bedwetting) – involuntary urination while asleep.
Stability and Storage: Imipramine hydrochloride, when heated to decomposition, emits toxic
fumes of nitroxides. It turns yellowish or reddish on exposure to light. Slight discoloration does
not affect potency, but marked discoloration is associated with loss of potency. Store the drug in
airtight containers. Protect from light. The powder absorbs insignificant amounts of moisture at
23°C at relative humidities up to 60%. Under more humid conditions, significant absorption
occurs.
164 Text Book of Pharmaceutical Chemistry
Marketed Preparations:
➢ Imipramine Hydrochloride Tablets USP 25 mg – Excellium Pharmaceutical
➢ Depsonil-25 (Imipramine Hydrochloride Tablets I.P.) – Cadila Healthcare Limited
(Zydus)
➢ IRA-75 (Imipramine Hydrochloride 75 mg and 25 mg Tablet) – Elikem Pharmaceuticals
Pvt. Ltd.
5.5.3 Fluoxetine
Brand Names: Prozac, Sarafem, Rapiflux, Selfemra, Act Fluoxetine, Symbyax
Fluoxetine (Proza) is a psychotropic drug used to treat major depressive disorder. It is a
conjugate base of a (R)-fluoxetine (1+). It is an enantiomer of a (S)-fluoxetine. The structural
formula of Fluoxetine is:
Chemical Name: N-methyl-3-phenyl-3-[4-(trifluoromethyl) phenoxy] propan-1-amine
Properties: Fluoxetine occurs as white to off-white crystalline solid. It is soluble in water,
methanol and chloroform; and insoluble in hexane, ethyl acetate and benzene. Melting point is
157.5°C to 158.7°C.
Uses:
➢ Prozac is effective in treating major depressive disorder and anxiety.
➢ It is used to treat obsessive-compulsive disorder (OCD). OCD is characterized by
unreasonable thoughts and fears (obsessions) that lead to compulsive behaviors.
➢ It is used for the treatment of post-traumatic stress disorder (PTSD). The PTSD is a
mental and behavioral disorder that can develop because of exposure to a traumatic event
such as child abuse and domestic violence.
➢ It is used for the treatment of bulimia nervosa (an eating disorder) and panic disorder.
➢ It is indicated in the treatment of premenstrual dysphoric disorder.
➢ It is indicated in the treatment of trichotillomania (also known as hair-pulling disorder) –
a condition that gives some people strong urges to pull out their own hair.
➢ It is used in cataplexy, obesity and alcohol dependence.
Storage and Stability: Stable at 40°C and 75% humidity in polyethylene bottles or foil packs for
at least five years.
Drugs Acting on Central Nervous System 165
Pharmaceutical Formulations: It is only available in an oral formulation available in liquid
form, tablet, and capsule. It is started at a dose of 20 mg per day.
➢ Fluoxetine capsule I.P. – 20 mg
➢ Fluoxetine capsule I.P. – 60 mg
➢ Fluoxetine suspension I.P. – 20 mg/5 mL
Marketed Preparations:
➢ Fluoxetine Capsule USP 20 mg – Taj Pharmaceuticals
➢ Prozac-20 (Fluoxetine 20 mg Lily Prozac, Tablet) – Chorus Pharmaceuticals
➢ Fluoxecap (Fluoxetine) Capsules USP 20 mg – Medico Remedies Limited
➢ Fluoxn-20 (Fluoxetine Hydrochloride Capsule I.P.) – Dewcare Concept Pvt. Ltd.
5.5.4 Venlafaxine
Brand Names: Effexor XR, Effexor
Venlafaxine structure is a tertiary amino compound that is N, N-dimethyl ethanamine
substituted at position 1 by a 1-hydroxycyclohexyl and 4-methoxyphenyl group. It is a member of
cyclohexanols, a tertiary alcohol, a tertiary amino compound and a monomethoxybenzene.
Venlafaxine is an anti-depressant belonging to a group of drugs called selective serotonin and
norepinephrine reuptake inhibitors (SSNRIs). The structural formula of Venlafaxine is:
Chemical Name: 1-[2-(dimethylamino)-1-(4-methoxyphenyl) ethyl]cyclohexan-1-ol
Properties: Venlafaxine occurs as off-white to white, crystalline powder that is soluble 572
mg/mL in water and melts at about 217°C.
Uses:
➢ Venlafaxine is used to treat major depressive disorder, anxiety and panic disorders.
➢ It is used off-label to treat migraine.
➢ It is used in diabetic neuropathy (nerve damage that is caused by diabetes), and hot
flashes.
➢ It is used in generalized anxiety disorder (GAD) and social anxiety disorder (social
phobia).
➢ It is used in the treatment of Panic disorder (panic attacks).
166 Text Book of Pharmaceutical Chemistry
Dosage Forms: It is available as both immediate-release and extended-release tablets. Extended-
release tablet (150 mg, 37 mg and 75 mg); oral tablet (100 mg, 25 mg, 37 mg, 50 mg and 75 mg);
and oral tablet extended release (25 mg).
Storage and Stability: Store the drug in airtight containers Protect from light. Venlafaxine
immediate-release suspensions, prepared in OraSeet simple syrup, are physically and
chemically stable for 28 days when stored in amber plastic bottles at either 5°C or 23°C.
Marketed Preparations:
➢ Venwell-75 (Venlafaxine Capsules) – Wellona Pharma Pvt. Ltd.
➢ Venx-150 (Venlafaxine Extended Release Capsule USP) – White Swan Pharmaceutical
➢ Venlafaxine 75 mg (Venlafaxine Hydrochloride Tablet) – Neuracle Lifesciences Pvt. Ltd.
5.5.5 Duloxetine
Brand Names: Cymbalta, Drizalma Sprinkle, Irenka
Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor generally used as an
anti-depressant and for neuropathic pain. It is known as a serotonin-norepinephrine reuptake
inhibitor (SNRI). The structural formula is:
Chemical Name: (3S)-N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-ylpropan-1-amine
Properties: Duloxetine hydrochloride is a white to slightly brownish white solid, which is
slightly soluble in water.
Uses: Duloxetine is indicated for the treatment of:
➢ Major depressive disorder
➢ Generalized anxiety disorder,
➢ Fibromyalgia, and neuropathic pain
➢ Chronic musculoskeletal pain.
Dosage Forms: Duloxetine is available in delayed-release capsule (20 mg, 30 mg, 40 mg and
60 mg).
Marketed Preparations:
➢ DELOXIT-20 (Duloxetine Hydrochloride 20 mg Tablets) – Psychocare Health Pvt. Ltd.
➢ DUXILA-30 (Duloxetine Gastro Resistant Tablets I.P. 30) – Dellwich Healthcare LLP
➢ Duloxetine 60 mg (Duloxetine Tablets) – Salvavidas Pharmaceutical Pvt. Ltd.