Mechanism of Action of GABA, Barbiturates, and Benzodiazepines

Introduction

• Presented by Mr. Ram Rao Fad, Assistant Professor at Maharashtra College of Pharmacy, Nilanga.
• Video focuses on the mechanism of action of GABA, barbiturates, and benzodiazepines.
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GABA Receptors Overview

• Types of GABA Receptors:
  • GABA A
  • GABA B (GPCR)
  • GABA C
• Focus on GABA A receptor, a ligand-gated chloride ion channel.

GABA-A Benzodiazepine Receptor Chloride Channel Complex

• Structure:
  • Pentameric transmembrane anion channel.
  • Composed of 5 subunits: alpha, beta, gamma, and sometimes delta, epsilon, theta, pi.
  • Common isoform: 2 alpha, 2 beta, 1 gamma subunit.
• Initially closed; opened by binding of agonists, primarily GABA.

Mechanism of GABA

• Primary Agonist: GABA (gamma-aminobutyric acid)
• Binds to the GABA-A receptor causing conformational changes, opening the channel.
• Effect:
  • Chloride ions enter the cell.
  • Increases negative voltage membrane potential (hyperpolarization).
  • Creates inhibitory post-synaptic potential (IPSP).
  • Inhibits action potential generation and impulse conduction, causing CNS depression.

Barbiturates Mechanism of Action

• Drugs: Phenobarbitone, Amobarbital, Secobarbital.
• Binding Site: Barbiturate site on alpha or beta subunits.
• Actions:
  • GABA-facilitatory: Increase duration of chloride channel opening, assisting GABA binding.
  • GABA-mimetic: At high concentrations, can directly open the channel.
  • Can also block excitatory neurotransmitter glutamate by blocking AMPA receptors.

Benzodiazepines Mechanism of Action

• Drugs: Diazepam, Oxazepam, Nitrazepam.
• Binding Site: Benzodiazepine receptor at alpha and gamma subunit interface.
• Action:
  • Increase frequency of chloride channel opening.
  • Only facilitate GABA binding, cannot open channel directly (no GABA-mimetic action).

Differences Between Barbiturates and Benzodiazepines

1. GABA-Facilitatory Action:
   • Barbiturates: Increase duration of opening.
   • Benzodiazepines: Increase frequency of opening.
2. Direct Channel Opening:
   • Barbiturates: Can open channel directly at high concentrations (GABA-mimetic action).
   • Benzodiazepines: Cannot open channel directly, even at high concentrations.

Conclusion

• Video covered the mechanism of action for GABA, barbiturates, and benzodiazepines.
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