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Benzodiazepines help reduce anxiety but they also cause sedation. A more effective drug would reduce anxiety without causing sedation. The experiment shown in Figure was performed in which the histidine was replaced by an arginine on either the α1 or α2 subunit of GABAA receptors. This substitution causes the subunit to become insensitive to benzodiazepines while retaining its sensitivity to GABA. Figure Q11-28
A. What happened to the α1(H101R) mice when they were given diazepam and what conclusion can be drawn about the α1 subunit?
B. What happened to the α2(H101R) mice when they were given diazepam and what conclusion can be drawn about the α2 subunit?
C. What does this tell you about designing a drug for anxiety?
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