Buspirone anxiolytic action

Two studies have indicated that the tricyclic antidepressant (TCA) imipramine may be as effective as BZDs in the treatment of GAD ( 58, 59). No studies longer than 8 weeks duration have been conducted, however, and imipramine s onset of anxiolytic action may be even slower than that of buspirone. Aithough adverse effects also may limit usefulness, its lack of dependence liability may make it an appropriate alternative in chronically anxious patients who also suffer from panic and depression. 

FIGURE 8—11. Serotonin 1A partial agonists such as buspirone may reduce anxiety by actions both at presynaptic somatodendritic autoreceptors (left) and at postsynaptic receptors (right). Presynaptic actions are more likely related to anxiolytic actions, and postsynaptic actions are perhaps more likely linked to side effects such as nausea and dizziness. 

Bodkin JA, Teicher MH. Fluoxetine may antagonize the anxiolytic action of buspirone. J Clin Psychopharmacol (1989) 9, 150. 

Anxiolytics are drugs used for the treatment of anxiety disorders. Apart from benzodiazpines, a frequently used anxiolytic is the 5HT1A (serotonin) receptor agonist buspiron, which has no sedative, amnestic or muscle-relaxant side effects, but whose action takes about a week to develop. Furthermore, it is less efficaceous than the benzodiazepines. Buspiron s mechanism of action is not fully understood. 

Buspirone (Buspar). The first nonsedating, nonbenzodiazepine specifically introduced as an anxiolytic, buspirone is FDA approved for the treatment of GAD. This medication acts as a partial agonist at the postsynaptic serotonin (5HT)-1A receptor. Like the antidepressants, buspirone has a delayed onset of action and effectively relieves the intrapsychic symptoms of GAD. Devoid of the muscle-relaxing properties of benzodiazepines, buspirone does not as effectively relieve the physical symptoms of GAD. Buspirone is not effective in the treatment of depression. Furthermore, its utility for the treatment of anxiety disorders other than GAD appears to be limited. 

Buspirone is an extremely specific drug that could possibly represent a new chemical class of anxiolytics—azaspirones. As an anxiolytic, its activity is equal to that of benzodiazepines however, it is devoid of anticonvulsant and muscle relaxant properties, which are characteristic of benzodiazepines. It does not cause dependence or addiction. The mechanism of its action is not conclusively known. It does not act on the GABA receptors, which occurs in benzodiazepine use however, it has a high affinity for seratonin (5-HT) receptors and a moderate affinity for dopamine (D2) receptors. Buspirone is effective as an anxiolytic. A few side effects of buspirone include dizziness, drowsiness, headaches, nervousness, fatigue, and weakness. This drug is intended for treatment of conditions of anxiety in which stress, muscle pain, rapid heart rate, dizziness, fear, etc. are observed in other words, conditions of anxiety not associated with somewhat common, usual, and everyday stress. Synonyms for buspirone are anizal, axoren, buspar, buspimen, buspinol, narol, travin, and others. 

Pharmacology Mechanism of action is unknown. It differs from benzodiazepines in that it does not exert anticonvulsant or muscle relaxant effects. It also lacks prominent sedative effects associated with more typical anxiolytics. Buspirone has effects on serotonin, dopamine, and norephinephrine. 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

In summary, buspirone is an effective generalized anxiety treatment that differs from conventional antianxiety drugs in speed of symptom reduction and types of symptoms affected. Although buspirone might seem to be the drug of choice for treatment of chronic anxiety, it has not displaced the use of benzodiazepines in the treatment of anxiety, perhaps because of its side-effect profile [dizziness, sedation, nausea], slow onset of action, and the opinion of some clinicians that its anxiolytic efficacy is less robust than that of benzodiazepines. Buspirone is accepted as an anxiolytic treatment much more widely in the United States than in most other countries [Kunovac and Stahl 1995]. 

Several drugs with novel chemical structures have been introduced more recently for use in sleep disorders. Zolpidem, an imidazopyridine, zaleplon, a pyrazolopyrimidine, and eszopiclone, a cyclopyrrolone (Figure 22-4), although structurally unrelated to benzodiazepines, share a similar mechanism of action, as described below. Eszopiclone is the (S) enantiomer of zopiclone, a hypnotic drug that has been available outside the United States since 1989. Ramelteon, a melatonin receptor agonist, is a new hypnotic drug (see Ramelteon). Buspirone is a slow-onset anxiolytic agent whose actions are quite different from those of conventional sedative-hypnotics (see Buspirone). 

Several drugs with novel chemical structures have been introduced recently. Buspirone is an anxiolytic agent that has actions different from those of conventional sedative-hypnotic drugs. Zolpidem and zaleplon, while structurally unrelated to benzodiazepines, share a similar mechanism of action. 

Buspirone is structurally unrelated to other anxiolytics and was the first nonbenzodiazepine to demonstrate efficacy in GAD. Its mode of action is unclear, although we know it suppresses 5HT neurotransmission through a selective activation of the inhibitory presynaptic 5HT1 -reactor. Buspirone has a tl of 7 h, and is metabolised in the liver it has an active metabolite that may accumulate over weeks. Twice daily dosing is suitable, with the usual range being 15-30 mg/d p.o., maximum 45 mg/d. 

Buspirone is generally less effective and slower in action than benzodiazepines emd does not improve sleep it does not benefit benzodiazepine withdrawal symptoms. The advantages are that it does not seem to cause dependence or withdrawal reactions and does not interact with alcohol. It appears to be less effective in patients who have previously received benzodiazepines and is therefore probably best used in benzodiazepine naive patients. A disadvantage is that useful anxiolytic effect is delayed for 2 or more weeks. 

Buspirone. The dominance enjoyed by the benzodiazepines is illustrated by the fact that no new anxiolytics were launched until buspirone (9)reached the market in 1986. Buspirone is a member of the azapirone class, and produces its therapeutic effects through partial agonism at 5HT-1A receptors. Buspirone is indicated and widely used for GAD, but has failed to show significant efficacy in other anxiety disorders (52). Although perhaps less consistently effective than the BZs, buspi-rone s improved safety profile provides the main point of differentiation between the two therapies. Buspirone causes less sedation, motor and cognitive impairment, and does not appear to be associated with any withdrawal syndrome. Drawbacks include a delayed onset of action (several weeks), and a reduced effect... 

Buspirone s anxiolytic mechanism of action is unknown. It is thought to exert its anxiolytic effect through 5-HTia partial agonist activity at the presynaptic 5-HT receptors by reducing the firing of 5-HT neurons. Unlike benzodiazepines, buspirone is effective for the cognitive symptoms of anxiety. ... 

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