09.05 Cell Signaling

There are not a lot of drugs used for their ability to interfere with the cell signaling of neurotransmitters, probably because it is usually easier to target the receptor for the neurotransmitter. Benzodiazepines (e.g. diazepam) are the main drugs used to treat anxiety and insomnia, and to cause sedation. The benzodiazepines potentiate the effects on an inhibitory neurotransmitter in the central nervous system by modifying its cell signaling. This inhibitory neurotransmitter is gamma (γ)-aminobutyric acid (GABA). There are cell surface receptors for GABA and there are two main types GABA_A and GABA_B. The GABA_A receptor is the one the benzodiazepines interact with. The GABA_A receptor has 5 subunits that form a Cl- channel (Figure 9.1). Benzodiazepines bind to a distinct binding site, the benzodiazepine binding site on the GABA_A receptor to potentiate the effect of GABA, which is to open the chloride channel, and the more chloride that goes through the channel, the bigger the inhibitory effect. Benzodiazepines have no effect alone, and are only effective when GABA is present.

Figure 9.1 Benzodiazepine binding site, GABA_A receptor and chloride channel (Copyright QUT, Sheila Doggrell)