HT1A Agonists

The azapirone class of drugs includes the 5HT1A agonist, buspirone (Figure 8), which also has weak dopaminergic activity.92 5HT1A receptors have opposing effects on the release of 5HT depending on whether they are located on pre-or postsynaptic sites, and it is hypothesized that the activation of the autoreceptors on the raphe nuclei contributes to the delayed onset of SSRIs in the clinic. Thus, agonism of the 5HT1A receptor (pre- and post-synaptically) could produce changes in brain 5HT systems that are similar to those seen following SSRI administration, but only in brain areas expressing the 5HT1A receptor. Buspirone was efficacious in several animal models of anxiety providing an impetus for its evaluation in a series of double-blind, placebo-controlled anxiety trials. These trials established the efficacy of buspirone, without accompanying neuroleptic side effects or abuse potential. Buspirone was the first non-BZ



Figure 7 Structures of SNRIs.

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