Buspirone anxiolytic activity

The anxiolytic agent buspirone (131) is notable for the fact that it does not interact with the receptor for the benzodiazepines. This difference in biochemical pharmacology is reflected in the fact that buspirone (131) seems to be devoid of some of the characteristic benzodiazepine side effects. The spiran function is apparently not required for anxiolytic activity. Alkylation of 3,3-dimethylglutarimide with dichlorobutane in the presence of strong base yields the intermedi-... 

Anxiolytic activity Several novel anxiolytics (e.g. buspirone, ipsapirone) are 5-HTia partial agonists 5-HT2 and 5-HT3 antagonists have anxiolytic properties... 

S-HTjc, and 5-HTj receptors may be especially involved in the serotonin system s response in anxiety. Most interest has focused around 5-HTj, drugs (buspirone, ipsapirone, gepirone, tandospirone, flesinoxan, and others]. Some preclinical data indicate that antagonists at S-HTj, S-HTj, and 5-HT3 receptors may also exert anxiolytic activity, but so far these findings have not been consistently confirmed in clinical trials. 

Buspirone. Hie initial compound in this series, buspir-one (BuSpar). has anxiolytic and antidepre.ssnnt activities and is a partial. iHTiA agonist. Its anxiolytic activity is reportedly due to its ability to diminish. -ITT release (via. SHTia agonism). High short-term synaptic levels of. S-HT ate characteri.stic of anxiety. Also, since it is a partial agoni.st. it can stimulate postsynaptie receptors when 5-HT levels are low in the synapse, as is the case in depression. A number of other spirones are in development as anxiolytics and antidepressants. ... 

Answer B. Buspirone has selective anxiolytic activity that is slow in onset The drug has no abuse liability and will not suppress withdrawal symptoms in patients who have become physically dependent on barbiturates, benzodiazepines, or ethanol. Bupropion is an antidepressant, also approved for management of dependence on nicotine. Baclofen is a spinal cord muscle relaxant that activates GABAfi receptors. Buprenorphine is a long-acting opioid analgesic with no effectiveness in GAD, and butabarbital is a barbiturate that may cause dependence. 

The 5-HT receptors in the hippocampus and other parts of the limbic system are primarily of the 5-HTia type. It is therefore tempting to speculate that drugs that display a high degree of selectivity for these receptor sites can selectively affect anxiety states. A breakthrough in that direction came with the discovery that buspirone, a drug with anxiolytic activity in humans, can help elucidate the role of 5-HT in anxiety. Buspirone, gepirone, and ipsapirone may therefore offer new therapeutic directions in the treatment of anxiety. 

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. 

Benzodiazepine anxiolytics and hypnotics lead to a decrease in alpha and an increase in beta activity in pharmaco-EEG trials. With regard to theta and delta activities, the results of different studies vary. Buspirone at the usual therapeutic doses induces no or only a very weak EEG effect (Greenblatt et al., 1994) and is thus differentiated from the benzodiazepine anxiolytics. 

Buspirone is an azapirone anxiolytic that acts as a partial 5-HT agonist. In contrast to the BZDs, this agent has no immediate effect on the anxiety seen in patients undergoing medical procedures (e.g., endoscopy, cardioversion). Further, it cannot be given parenterally, because the drug is not available in an i.v. or i.m. formulation. Buspirone does not produce disinhibition euphoria and even in high doses has not been found to have antipsychotic activity. 

Buspirone Mechanism uncertain Partial agonist at 5-HT receptors but affinity for D2 receptors also possible Slow onset (1-2 weeks) of anxiolytic effects t minimal psychomotor impairment—no additive CNS depression with sedative-hypnotic drugs Generalized anxiety states Oral activity forms active metabolite short half-life Toxicity Tachycardia paresthesias t gastrointestinal distress Interactions CYP3A4 inducers and inhibitors... 

In 10 healthy volunteers, fluvoxamine (100 mg/day for 5 days) significantly increased the peak concentrations of the anxiolytic drug buspirone. Concentrations of the active metabolite, l-(2-pyrimidinyl)-piperazine, were reduced (23). These effects were probably mediated through inhibition of CYP3A4 by fluvoxamine. 

---