Benzodiazepines are double-ringed positive allosteric modulators of the GABA receptors in the CNS. They:

  • Bind to the α/γ interface of the receptor, increasing affinity of the receptor for GABA
  • This leads to hyperpolarisation of the cell membranes and decreased neuronal transmission
    The mechanism varies between receptors:
    • GABAA is a ligand gated post-synaptic Cl- ion channel
      Activation increases Cl- conductance via increasing frequency of channel opening.
    • GABAB is a pre- and post-synaptic G-protein coupled receptor
      Activation increases K+ conductance.

Common Features of Benzodiazepines

Property Action
Uses Sedation, anxiolysis, hypnotic, anticonvulsants, amnestic, muscle relaxation
Distribution Highly lipid soluble and protein bound, very low VD
Metabolism Generally active metabolites.
Elimination Renal elimination of active and inactive metabolites.
Resp ↓ VT, ↑RR, apnoea.
CVS SVR, ↓SBP, ↓ DBP, ↑HR. Typically stable CO.
CNS Hypnosis, sedation, anterograde amnesia, anticonvulsant, ↓ CBF. ↓ MAC.
MSK Skeletal muscle relaxation.
Metabolic ↓ Adrenergic stress response.

Comparison of Benzodiazepines

Property Midazolam Diazepam Clonazepam
Physicochemical pKa 6.5. Structure is dependent on surrounding pH - at a pH < 4 its ring structure opens and it becomes water soluble. 40% propylene glycol.
Route of Administration PO/IV/IM. PO/IV/IM. PO.
Absorption 50% PO bioavailability. Good PO bioavailability.
Distribution VD, 95% protein bound. 95% protein bound.
Metabolism Partially metabolised to oxazepam and 1-α-hydroxy-midazolam. Clearance Hepatic to all active metabolites including oxazepam, temazepam, and des-methyl-diazepam (has t1/2β up to 100 hours). Hepatic to inactive metabolites.
Elimination t1/2β 2-4 hours, prolonged with cirrhosis, CHF, obesity and in the elderly. t1/2β 20-45 hours.


  1. Smith S, Scarth E, Sasada M. Drugs in Anaesthesia and Intensive Care. 4th Ed. Oxford University Press. 2011.
  2. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  3. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
  4. Rang HP, Dale MM, Ritter JM, Flower RJ. Rang and Dale's Pharmacology. 6th Ed. Churchill Livingstone.
Last updated 2019-07-18

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