Disease relevance of buspirone

• High-dose buspirone in case of tardive dyskinesia [1].
• Treatment of cerebellar ataxia with buspirone: a double-blind study [2].
• Buspirone in treatment of premenstrual syndrome [3].
• Panic and hypertension associated with single dose of buspirone [4].
• Buspirone for anxiety disorders in patients with severe lung disease [5].

Psychiatry related information on buspirone

• Buspirone metabolite and panic attacks [6].
• Short-term buspirone treatment in disinhibition with dementia [7].
• Buspirone treatment of Tourette's syndrome [8].
• RESULTS: Buspirone therapy was associated with greater retention in the 12-week treatment trial, reduced anxiety, a slower return to heavy alcohol consumption, and fewer drinking days during the follow-up period [9].
• Effect of buspirone on withdrawal symptoms associated with smoking cessation [10].

High impact information on buspirone

• Serotonin receptors, buspirone, and premenstrual syndrome [11].
• Effect of buspirone on prolactin secretion is not mediated by 5-HT-1a receptor stimulation [12].
• It may be that buspirone and benzodiazepine drugs stimulate GH secretion by a common mechanism that is related to their anxiolytic actions [13].
• Buspirone attenuates synaptic activation of hippocampal pyramidal cells [14].
• Concurrent with this attenuation of the EPSP, buspirone decreases the excitability of afferent fibers in the stratum radiatum as evidenced by conduction slowing, increased refractory period, and decreased ability to generate repetitive impulses [14].

Chemical compound and disease context of buspirone

• In a double-blind, crossover study, 13 fluoxetine-treated patients with obsessive-compulsive disorder were given adjuvant buspirone and placebo for 4 weeks each [15].
• Adjunctive buspirone in benzodiazepine treatment of four patients with panic disorder [16].
• It is suggested that combining small doses of buspirone to diazepam does not cause any additional decrement in psychomotor performance [17].
• CONCLUSIONS: This study suggests that buspirone, but not sumatriptan, the selective agonist of 5-HT1-like receptors, causes miosis in humans by activation of 5-HT1A receptors, possibly located in the central nervous system where they inhibit iris sympathetic pathways [18].
• Scientific evidence regarding the drug abuse potential of buspirone and gepirone is reviewed [19].

Biological context of buspirone

• Whereas 5-HT application leads to a rapid hyperpolarization and decreased input resistance in pyramidal cells, buspirone has no measurable effects on membrane potential and input resistance [14].
• The pharmacokinetics of buspirone were not significantly different in men and women or in individuals 21 to 40 years old compared with those over 65 years of age [20].
• Food increases the bioavailability of buspirone by decreasing first-pass metabolism; absorption is not markedly altered [20].
• Neither buspirone nor diazepam had any effect on blood pressure, pulse and respiratory rates, or body temperature [21].
• RESULTS: Verapamil and diltiazem increased the area under the buspirone plasma concentration-time curve [AUC (0-infinity)] 3.4-fold (p < 0.001) and 5.5-fold (p < 0.001), respectively [22].

Anatomical context of buspirone

• CONCLUSION: The study shows that buspirone modulates the immune system and leads to changes in the CD4 and CD8 T-cell numbers, functional capacity, cell maturation and viral load [23].
• Furthermore, preclinical studies have shown that buspirone does not possess anticonvulsant or muscle relaxant properties and does not interact significantly with central nervous system depressants [24].
• Development of "flu-like' symptoms, so severe that two patients withdrew from the study and two patients ceased medication before time, was a clinical indication of modulation of the immune system by buspirone [23].
• (R)-8-OH-DPAT, (S)-8-OH-DPAT, and buspirone stimulated [35S]GTPgammaS binding in hippocampus by 340%, 140%, and 78%, with EC50 values of 71, 51, and 132 nM [25].
• This incorporation could be blocked when membranes were incubated with 1 microM of several agents that have high affinity for 5-HT1A sites [5-HT, 8-hydroxy-2-(di-n-propylamino)tetraline, TVX Q 7821, spiperone, buspirone, d-lysergic acid diethylamide, metergoline] [26].

Associations of buspirone with other chemical compounds

• In man, buspirone hydrochloride at doses of 30, 60, and 90 mg orally significantly elevated plasma prolactin (PRL) and growth hormone (GH) concentrations [13].
• Spontaneous 5-HT1A receptor activity was partially attenuated by 5-HT1A receptor partial agonists with anxiolytic activity (e.g. buspirone and flesinoxan) but was not altered by full agonists or antagonists [27].
• Obsessive-compulsive disorder, fluoxetine, and buspirone [28].
• Not only does the lack of effect of buspirone on the Amphetamine and Morphine-Benzedrine Group subscales indicate lack of a euphorigenic property, but the score on the Lysergic Acid Diethylamide subscale, especially in the 40-mg group, suggests a dysphorigenic property at high doses [21].
• By contrast, buspirone is 16-fold weaker at dopamine (D2) receptors (IC50 = 380 nM), whereas TVX Q 7821 is 6-fold less potent at alpha-adrenergic1 sites (IC50 = 58 nM) [29].

Gene context of buspirone

• The effect of buspirone on prolactin and growth hormone secretion in man [13].
• Moreover, both location and topography of putative binding sites for buspirone analogues are different at 5-HT1A and 5-HT2A receptors [30].
• The overall metabolism rate of 5 microM buspirone by CYP3A4 was 18-fold greater than that by CYP2D6 and 35-fold greater than that by CYP3A5 [31].
• In a panel of HLMs from 16 donors, buspirone metabolism correlated well CYP3A activity (r2 = 0.85-0.96, rho < 0.0005), but not the activities of other P450 isoforms [31].
• The metabolism rates of buspirone in CYP2D6 poor-metabolizer genotype HLMs were comparable to those in pooled HLMs [31].

Analytical, diagnostic and therapeutic context of buspirone

• These issues are discussed herein, using the clinical trials of buspirone, a new, nonsedating antianxiety agent, as a model for the process of drug selection [32].
• The single-blind study, conducted in 23 outpatients, consisted of 28 days of buspirone treatment followed by four days of placebo treatment [33].
• Buspirone was not removed by hemodialysis [20].
• A small, transient pupillary constriction was evident in the 20- and 40-mg buspirone groups, but it dissipated within two hours after dosing [21].
• Buspirone did not alter the EEG or DSST performance but did increase self-ratings of sedation and feeling "spacey" and impaired memory function; these effects generally were quantitatively less than with triazolam [34].

References