azapirones

a·za·pir·ones

(ā'za-pī'rōnz),
Anxiolytics acting through agonist action at serotonin 1-A receptors.
References in periodicals archive ?
BuSpar is a prototypic member of a unique class of anxiolytics, the azapirones, and has been demonstrated to effectively relieve the symptoms of anxiety without producing the sedation, drug dependence, or withdrawal concerns associated with other anxiolytics.
PRX-00023 is targeting a significant unmet medical need for a selective 5-HT1A agonist used in the treatment of depression that avoids the sexual dysfunction, withdrawal symptoms and sleep disturbances typically associated with selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs), lacks the addictive and sedative effects of the benzodiazepines, and does not have the slow onset, short half-life, and side effects of a chemical class of 5-HT1A agonists called azapirones.
30] Buspirone (BuSpar) and related azapirones are thought to exert anxiolytic effects by action at the 5-[HT.
PRX-00023 is targeting a significant unmet medical need and commercial opportunity for a selective, once-daily, 5-HT1A agonist used in the treatment of depression that avoids the sexual dysfunction, withdrawal symptoms and sleep disturbances typically associated with selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs), lacks the addictive and sedative effects of the benzodiazepines, and does not have the slow onset, short half-life, and side effects of a chemical class of 5-HT1A agonists called azapirones.
With PRX-00023, which entered human clinical trials in February 2004, the company is targeting a significant unmet medical need and commercial opportunity for a selective, once-daily, agonist of the specific GPCR known as 5-HT1A that avoids the sexual dysfunction and sleep disorders associated with SSRIs, lacks the addictive and sedative effects of the benzodiazepines, and does not have the slow onset, short half-life, and side effects of a chemical class of 5-HT1A agonists called azapirones (most of which have failed in clinical development due to poor tolerability at effective doses).
However, most of these drugs belong to a chemical class of drugs called azapirones, and their development has been hindered by poor tolerability at therapeutic doses, need for dosing up to three times daily, and by the requirement of gradual dose escalation to effective doses because of side effects such as nausea, dizziness, and restlessness which are thought to be caused by azapirones binding to non-5-HT1A GPCRs.
In contrast, PRX-00023 is designed to have minimal affinity for the GPCRs believed to be associated with the side effects of 5-HT1A agonists that are in the azapirone chemical class, and to have a more convenient dosing profile than azapirones.
However, most of these drugs belong to a chemical class of drugs called azapirones, and their development has been hindered by poor tolerability at therapeutic doses, need for dosing up to three times daily, and the requirement of gradual dose escalation to effective doses because of side effects such as nausea, dizziness, and restlessness which are thought to be caused by azapirones binding to non-5-HT1A GPCRs.
However, most of these drugs belong to a chemical class of drugs called azapirones and their development has been hindered by poor tolerability at therapeutic doses, rapid metabolism, and the requirement of slow dose escalation to effective doses because of nausea and lightheadedness, which are thought to be caused by their binding to off-target GPCRs.
In contrast, PRX-00023 is designed to be highly selective for the 5-HT1A receptor and has minimal affinity for the GPCRs believed to be associated with the side effects of 5-HT1A agonists that are in the azapirone chemical class, and to have a more convenient dosing profile than azapirones.
However, most of these drugs belong to a chemical class of drugs called azapirones and their development has been hindered by poor tolerability at therapeutic doses, rapid metabolism, resulting in a short half-life and, therefore, requiring multiple daily dosing, and the requirement of slow dose escalation to effective doses because of nausea and lightheadedness, which are thought to be caused by their binding to off-target G-Protein Coupled Receptors (GPCRs).
This discovery pertains specifically to the systemic use of a metabolite, known as 6-hydroxy-buspirone, which is produced by the body after administration of non-addictive anxiolytic agents known as azapirones, of which BuSpar is the most widely prescribed.