Classifications of Benzodiazepine based on the structure, halflife, onset and Receptor slectivity

🧠 Classification of Benzodiazepines and Benzodiazepine-like Drugs | Comprehensive Pharmacology Lecture

This SlideShare provides an in-depth, structured classification of Benzodiazepines (BZDs) and Benzodiazepine-like drugs (Z-drugs), integrating chemical, pharmacokinetic, pharmacodynamic, and clinical perspectives. Ideal for pharmacology students, educators, and exam preparation (SPLE, NAPLEX, GPAT, or university exams).

🔬 Content Overview:

A. Based on Chemical Structure:

1,4-Benzodiazepines: Classical agents like Diazepam, Lorazepam, and Clonazepam.

1,5-Benzodiazepines: Clobazam and analogues with reduced sedation and greater anxiolysis.

Triazolo- and Imidazo-benzodiazepines: Alprazolam, Midazolam, and related agents with enhanced potency and rapid onset.

Thieno & Other Heterocyclic Derivatives: Etizolam, Tofisopam, and other atypical or non-GABAergic variants.

Non-Benzodiazepine but Benzodiazepine-like Drugs (Z-drugs): Zolpidem, Zaleplon, and Eszopiclone—selective hypnotics.

B. Based on Onset & Duration of Action:
Categorized into ultra-short, short, intermediate, and long-acting agents with clinical timing relevance.

C. Based on Half-life:
Detailed half-life classification for clinical and dosing optimization.

D. Based on Clinical Application:
Covers anxiolytics, hypnotics, anticonvulsants, muscle relaxants, and agents for alcohol withdrawal or procedural sedation.

E. Based on Metabolism:
Highlights Phase I and Phase II pathways—crucial for hepatic safety, geriatric pharmacology, and drug accumulation risk.

F. Based on Receptor Selectivity:
Distinguishes BZ₁ (α₁-selective) hypnotics from non-selective and partial agonists, emphasizing receptor-level pharmacodynamics.

⚗️ Key Features:

Mechanism-linked classification for deeper conceptual understanding.

Integration of Goodman & Gilman, Katzung, and KD Tripathi perspectives.

Clinical implications explained for each subgroup.

Includes classical benzodiazepines and newer analogues (Etizolam, Remimazolam).

🎯 Ideal For:

Pharmacy and medical students

Pharmacology educators and researchers

SPLE, USMLE, and NAPLEX aspirants

Clinicians revising sedative-hypnotic pharmacotherapy

Author’s Note:
This presentation bridges chemical structure–activity relationships (SAR) with clinical pharmacology, offering a unified framework to understand benzodiazepine diversity, metabolism, and therapeutic role

1. Baasir Umair (MPhil in Pharmacology, Lecturer at SCPS, Swat

1

Classification of Benzodiazepines and Benzodiazepine-like Drugs
A. Based on the chemical structure
Chemistry Drugs Structural Characteristics
1,4-Benzodiazepines Diazepam, Chlordiazepoxide, Lorazepam,
Oxazepam, Temazepam, Flurazepam, Clonazepam,
Nitrazepam, Clorazepate dipotassium, Nordazepam,
Desmethyldiazepam, Prazepam, Quazepam,
Halazepam, Brotizolam, Medazepam, Pinazepam,
Camazepam, Nimetazepam, Flunitrazepam,
Diclazepam, Delorazepam, Mexazolam,
Loprazolam, Loflazepate, Clotiazepam (thieno
analogue)
- Two nitrogen atoms at positions
1 and 4 of the diazepine ring. -
Represent the classical
benzodiazepines. - Many
(Diazepam, Lorazepam,
Clonazepam, Nitrazepam,
Chlordiazepoxide) are included
in KD Tripathi.
1,5-Benzodiazepines Clobazam, Arfendazam, Cloxazolam Nitrogens at positions 1 and 5
instead of 1 and 4 → less
sedative, more anxiolytic.
Clobazam (Tripathi) widely used
as an adjunct in epilepsy.
Triazolo-
benzodiazepines
(Triazole fused at
1,2 positions)
Alprazolam, Triazolam, Estazolam, Brotizolam,
Lormetazepam, Etizolam (technically a
thienotriazolodiazepine), Adinazolam, Haloxazolam,
Flutazolam, Uldazepam, Triflubazam
Presence of an additional triazole
ring enhances potency and
lipophilicity → faster onset.
Alprazolam (Tripathi) is most
widely prescribed.
Imidazo-
benzodiazepines
Midazolam, Loprazolam, Flumazenil (antagonist),
Ro48-6791 (Remimazolam)
Contains imidazole ring, confers
pH-dependent solubility: water-
soluble in acidic solution, lipid-
soluble at physiological pH →
rapid onset.
Thieno- and other
Heterocyclic
Benzodiazepine
analogues
Etizolam, Clotiazepam, Bentazepam, Tofisopam,
Thienodiazepam, Cinolazepam, Adinazolam,
Flutazolam
Thienodiazepines replace
benzene ring with thiophene ring
(e.g., Etizolam). Tofisopam is an
atypical benzodiazepine (non-
GABAergic).
Non-
benzodiazepine but
Benzodiazepine-like
(Z-drugs / Others)
Zolpidem, Zaleplon, Eszopiclone, Zopiclone,
Indiplon, Pagoclone, Abecarnil, Bretazenil,
Imidazenil, Suriclone
Structurally distinct but bind
BZ₁/BZ₂ sites on GABAₐ
receptor. Shorter half-life,
selective for sleep induction.
B. Based on onset of action and Duration of Action
Name Drugs Onset / Duration
Ultra-short acting
(1–3 h)
Midazolam, Triazolam, Remimazolam Rapid IV/oral onset, short
duration

2. Baasir Umair (MPhil in Pharmacology, Lecturer at SCPS, Swat

2

Short-acting (3–8
h)
Alprazolam, Lorazepam, Oxazepam,
Temazepam, Brotizolam, Etizolam
Intermediate onset
Intermediate-
acting (8–24 h)
Nitrazepam, Estazolam, Clobazam,
Lormetazepam, Adinazolam
Moderate duration
Long-acting (> 24
h)
Diazepam, Chlordiazepoxide, Flurazepam,
Clonazepam, Prazepam, Quazepam,
Clorazepate, Nordazepam
Delayed onset, prolonged
effects (active
metabolites)
C. Based on the Half-life
Type Half-life
(t₁/₂)
Drugs
Ultra-short < 3 h Midazolam, Triazolam, Remimazolam
Short 3–8 h Lorazepam, Oxazepam, Temazepam, Alprazolam, Etizolam
Intermediate 8–24 h Nitrazepam, Estazolam, Clobazam, Lormetazepam
Long > 24 h Diazepam, Chlordiazepoxide, Flurazepam, Clonazepam, Prazepam,
Quazepam, Clorazepate, Nordazepam
D. Based on Clinical Application
Indication Drugs
Anxiolytics Diazepam, Lorazepam, Alprazolam, Oxazepam, Clorazepate,
Chlordiazepoxide, Clobazam, Etizolam
Hypnotics / Sedatives Temazepam, Triazolam, Nitrazepam, Flurazepam, Lormetazepam, Estazolam,
Brotizolam
Anticonvulsants Diazepam, Lorazepam, Clonazepam, Clobazam, Nitrazepam, Midazolam
Muscle Relaxants Diazepam
Pre-anesthetic / Procedural
Sedation
Midazolam, Diazepam
Alcohol Withdrawal Chlordiazepoxide, Diazepam, Lorazepam
Atypical (Non-GABAergic) Tofisopam
E. Based on Metabolism
Type of Metabolism Drugs Importance
Phase I oxidative
metabolism → active
metabolites
Diazepam → desmethyldiazepam →
oxazepam; Chlordiazepoxide; Flurazepam;
Prazepam; Clorazepate
Long-acting,
accumulation
possible

3. Baasir Umair (MPhil in Pharmacology, Lecturer at SCPS, Swat

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Direct Phase II
glucuronidation (no active
metabolites)
Lorazepam, Oxazepam, Temazepam Safe in hepatic
impairment and
elderly
Rapid metabolism / ester
hydrolysis
Midazolam, Remimazolam Very short half-life;
anesthesia use
F. Based on selectivity
Selectivity Drugs Effect
BZ₁ (α₁ subtype
selective)
Zolpidem, Zaleplon, Eszopiclone Hypnotic, minimal muscle relaxation or
anticonvulsant activity
Non-selective (BZ₁
+ BZ₂)
Diazepam, Lorazepam,
Clonazepam, Midazolam,
Alprazolam
Broad CNS depressant action
Partial agonists /
Modulators
Bretazenil, Abecarnil, Imidazenil Experimental; less
tolerance/dependence