Specific Benzodiazepine Receptors

The BZ receptor has been classified into several types, based on α subunit isoforms and clinical effects related to each type. The BZ1 receptor contains the α1 isoform. The BZ1 receptor is highly concentrated in the cortex, thalamus, and cerebellum; it is responsible for the BZs’ sedative effects and anterograde amnesia and for some of the anticonvulsive effects of diazepam. Sixty percent of GABA-A receptors contain the α1 subunit. Therefore, amnesia is a common side effect of BZ use because the majority of GABA-A receptors contain the BZ1 receptor responsible for amnesia. A major factor in predicting amnesia risk is lipid solubility; the greater the lipid solubility, the greater the risk of amnesia. BZs with high lipid solubility have higher absorption rates and faster onset of clinical effects than BZs with low lipid solubility.

BZ2 receptors contain the α2 isoform and mediate the anxiolytic and, to a large extent, the myorelaxant effects of BZs. BZ2 receptors are highly concentrated in areas such as the limbic system, motor neurons, and the dorsal horn of the spinal cord. The anxiolytic effects of BZs are believed to be mediated through BZ2 receptors located in the limbic system, and myorelaxant properties are mediated via α2-containing receptors in the spinal cord and motor neurons. Not all BZs interact with the same type of BZ receptor or with equal affinity to a specific receptor. These differences in α subunit isoforms, BZ receptor type affinity, and location within the central nervous system account for the different effects of the various BZs.