Sedative & Hypnotics

 

Sedative and Hypnotics

Sedative

Drugs that decrease activity of the central nervous system (CNS), producing a calming effect. To Reduce anxiety, agitation, and excitement without necessarily causing sleep.

Hypnotics

Drugs that induce and maintain sleep by depressing the CNS more strongly than sedatives. To Facilitate onset of sleep and prolong its duration.

Classification

A. Barbiturates (Enhance GABA-A receptor activity (increase duration of Cl⁻ channel opening)

• Phenobarbital, 
• Pentobarbital, 
• Thiopental

B. Benzodiazepines (Bind to BZ site on GABA-A receptor, increase frequency of Cl⁻ channel opening)

• Diazepam
• Lorazepam
• Midazolam
• Temazepam

C. Non-benzodiazepine Hypnotics (Z-drugs) (Act selectively on GABA-A α1 subunit → strong hypnotic effect, minimal anxiolytic effect)

• Zolpidem 
• Zaleplon
• Eszopiclone

D. Melatonin Receptor Agonists (Stimulate MT1, MT2 receptors in the suprachiasmatic nucleus → regulate circadian rhythm)

• Ramelteon
• Tasimelteon

E. Antihistamines (H1 Blockers)(Produce sedation due to CNS H1 blockade)

• Diphenhydramine
• Hydroxyzine

F. Miscellaneous

• Chloral hydrate (older hypnotic)
• Clomethiazole

                                             -:Diazepam:-

 Chemical Name

7-chloro-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Chemical Structure

It has a benzodiazepine ring fused with a benzene ring.

Key groups:

• 7-chloro substitution (enhances potency)
• 5-phenyl group (increases activity)
• N-methyl group (affects pharmacokinetics)

Stability Conditions

• Diazepam is sensitive to light (photodegradation occurs).
• Stable in a dry form (tablet/powder).
• Aqueous solutions (like injections) are less stable, especially if exposed to light or heat.
• Hydrolysis occurs in acidic/alkaline conditions.

Storage Conditions

• Store at room temperature (20–25°C).
• Protect from light and moisture (amber-colored containers are used).
• Avoid freezing injectable formulations.
• Keep in tightly closed containers.

 Brand Names

• Valium 
• Calmpose
• Dizipam
• Zepose
• Stesolid

Medical Uses

1. Anxiety disorders (short-term management)
2. Insomnia (short-term, for sleep induction)
3. Muscle spasms & spasticity (e.g., in cerebral palsy, tetanus)
4. Seizures & status epilepticus (IV/rectal diazepam)
5. Pre-medication before surgery/anesthesia (sedative + amnesic effect)
6. Alcohol withdrawal syndrome (to prevent seizures, agitation)

                                                            -: Alprazolam:-

Chemical Name: 8-Chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine

Molecular Formula: C₁₇H₁₃ClN₄

Molecular Weight: 308.76 g/mol

Chemical Structure

Alprazolam belongs to the triazolobenzodiazepine class.
Structure features:

• Benzodiazepine ring system
• Triazole ring fused to the diazepine ring
• A phenyl substituent at position 6
• Substituted with a chloro group at position 8

Stability Conditions

• Stable under normal environmental conditions.
• Sensitive to: Light and moisture (can degrade with prolonged exposure).
• Shelf-life: Usually 2–5 years, depending on formulation.

Storage Conditions

• Store in a cool, dry place.
• Keep below 25 °C (room temperature).
• Protect from light and moisture.
• Store in tightly closed containers.
• Keep out of reach of children (due to abuse potential).

Brand Names

• Xanax (most common, Pfizer)
• Alprax (India)
• Restyl
• Niravam (orally disintegrating tablet)

 Medical Uses

Alprazolam is used primarily for CNS disorders-

• Anxiety disorders
• Panic disorder (with or without agoraphobia)
• Generalized Anxiety Disorder (GAD)
• Short-term relief of anxiety symptoms
• Adjunct for depression-associated anxiety

                                                    -:Nitrazepam:-

Chemical Name

5-(2-nitrophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Chemical Structure

Belongs to the benzodiazepine class.

Structure: A 1,4-benzodiazepine ring substituted with:

• Nitro group (-NO₂) at position 5 (2-nitrophenyl)
• Chloro group (-Cl) at position 7
• Keto group (=O) at position 2

Stability Condition

• Stable under normal temperature and pressure.
• Sensitive to light → decomposes on prolonged exposure.

Avoid contact with strong oxidizing agents.

Storage Condition

• Store in airtight, light-resistant containers.
• Temperature: 15–30 °C (room temperature).
• Protect from moisture and light.

Brand Names

• Mogadon 
• Alodorm
• Insomin

Uses

• Short-term treatment of severe insomnia
• As a sedative and anxiolytic
• Pre-anesthetic medication in some cases
• May be used in epilepsy (myoclonic and infantile spasms, adjunct therapy)

                                                                 -:Phenobarbital:-

Chemical Name: 5-ethyl-5-phenylbarbituric acid
IUPAC Name: 5-ethyl-5-phenyl-1,3-diazinane-2,4,6-trione
Molecular Formula: C₁₂H₁₂N₂O₃
Molecular Weight: 232.24 g/mol

Chemical Structure

A barbituric acid ring (pyrimidine nucleus) with substitutions:

• Ethyl group (-CH₂CH₃) at position 5
• Phenyl group (-C₆H₅) at position 5

          O

          ||

     N—C——CH2CH3

     |       |

   O=C       C=O

     |       |

     N——C6H5

          ||

          O

Stability Condition

• Stable under normal conditions.
• Sensitive to light and moisture.
• Aqueous solutions may undergo slow hydrolysis.

Storage Condition

• Store in a well-closed, light-resistant container.
• Protect from moisture and excessive heat.
• Recommended storage temperature: 15–30 °C (room temperature).

Brand Names

• Gardenal
• Luminal
• Solfoton
• Phenobarbitone 

Uses

• Anticonvulsant – treatment of epilepsy (generalized and partial seizures).
• Sedative-hypnotic – used for sedation and to induce sleep (rarely used today due to safer alternatives).
• Pre-anesthetic medication – to reduce anxiety before surgery.
• Treatment of neonatal jaundice – induces liver enzymes to increase bilirubin metabolism.
• Emergency management of status epilepticus when benzodiazepines are ineffective.