At the GABA-A chloride channel, the electrophysiological distinction between barbiturates and benzodiazepines is that barbiturates:

• A Increase the duration of chloride channel opening, while benzodiazepines increase its frequency ✓
• B Increase the frequency of chloride channel opening, while benzodiazepines increase its duration
• C Block the chloride channel directly, while benzodiazepines open it independently of GABA
• D Act identically to benzodiazepines but bind at the same allosteric site

Explanation

Barbiturates prolong the open state of the GABA-gated chloride channel (increased duration), whereas benzodiazepines increase the frequency of channel opening events. Both require GABA to be present. Because barbiturates can also open channels directly at high concentrations and have a narrow therapeutic index, they are far more dangerous in overdose than benzodiazepines, whose effect is capped by available GABA.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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