Azapirone

Azapirones are a class of

The azapirones include the following agents:[11]

Medical uses

Azapirones have shown benefit in general anxiety^[14] and augmenting SSRIs in social anxiety^[15] and depression.^[16] Evidence is not clear for panic disorder^[17] and functional gastrointestinal disorders.^[18]

Tandospirone has also been used to augment antipsychotics in Japan as it improves cognitive and negative symptoms of schizophrenia.^[19] Buspirone is being investigated for this purpose as well.^[20][21]

Side effects

Side effects of azapirones may include dizziness, headaches, restlessness, nausea, and diarrhea.^[4][22]

Azapirones have more tolerable adverse effects than many other available anxiolytics, such as

Buspirone was originally classified as an azaspirodecanedione, shortened to azapirone or azaspirone due to the fact that its chemical structure contained this moiety, and other drugs with similar structures were labeled as such as well. However, despite all being called azapirones, not all of them actually contain the azapirodecanedione component, and most in fact do not or contain a variation of it. Additionally, many azapirones are also pyrimidinylpiperazines, though again this does not apply to them all.

Drugs classed as azapirones can be identified by their -spirone or -pirone suffix.^[24]

Pharmacology

Pharmacodynamics

On a

• full agonists
  )
• 5-HT_2A receptor (as inverse agonists)
• D₂ receptor (as antagonists
  or partial agonists)
• α₁-adrenergic receptor
  (as antagonists)
• α₂-adrenergic receptor
  (as antagonists)

5-HT_1A receptor partial agonists have demonstrated efficacy against depression in rodent studies and human clinical trials.^{[37][38][39][40]} Unfortunately, however, their efficacy is limited and they are only relatively mild antidepressants. Instead of being used as monotherapy treatments, they are more commonly employed as augmentations to serotonergic antidepressants like the SSRIs.^{[6][7][8][9][10]} It has been proposed that high intrinsic activity at 5-HT_1A postsynaptic receptors is necessary for maximal therapeutic benefits to come to prominence, and as a result, investigation has commenced in azapirones which act as 5-HT_1A receptor full agonists such as alnespirone and eptapirone.^{[41][42][43][44]} Indeed, in preclinical studies, eptapirone produces robust antidepressant effects which surpass those of even high doses of imipramine and paroxetine.^{[41][42][43][44]}

Comparison of binding profiles

Pharmacokinetics

Azapirones are poorly but nonetheless appreciably