Buspirone anxiolytics

The pharmacological profile of buspirone in both animals and humans differs substantially from that of the ben2odia2epine anxiolytics. Buspirone lacks anticonvulsant, myorelaxant, and hypnotic effects. It also produces less sedation resulting in less psychomotor impairment in conjunction with... 

B.4.2.2 Nonbenzodlazeptnes GG-NPD was used by Kivisto et al. (1999) to quantitate the nonbenzodiazepine anxiolytic buspirone and its major metabolite, l-(2-pyrimidinyl)-piperazine, using separate extraction methods and separate assays. The hmit of quantification in plasma for both compounds was 0.2 ng/mL, which makes this assay useful for pharmacokinetic studies of this compound (Kivisto et al., 1999). A rapid, simple method for analysis of buspirone in rat brain requiring a single extraction step followed by GC-NPD has also been described (Lai. et al., 1997). 

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. A nonbenzodiazepine anxiolytic, buspirone is an effective treatment for generalized anxiety disorder but not other anxiety disorders. There are as yet no published controlled studies of buspirone for PTSD, though a small open label series suggested it might be effective for the core symptoms of PTSD. In the absence of more definitive evidence regarding its effectiveness, we do not routinely use buspirone when treating PTSD. 

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. 

Greenblatt, D J., Harmatz, J.S., Gonthro, T.A., et a/. Distinguishing a benzodiazepine agonist ( triazolam) from a nonagonist anxiolytic (buspirone) by electroencephalography kinetic-dynamic studies. CHn. Pharmacol. Ther. 56, 100— 111, 1994. 

Other than slow taper, no consistently effective treatment to alleviate withdrawal symptoms has been reported. Although several compounds have been studied (e.g., b-blockers, clonidine, carbamazepine, abercamil, ondansetron), results have been contradictory ( 250). Carbamazepine, however, may be useful in seizure-prone patients (251). Valproate (VPA) has also been reported to benefit patients undergoing BZD discontinuation after long-term dependence ( 252), which may be related to VPA s potential anxiolytic properties, its ability to alleviate withdrawal phenomena, or both. The azaspirone anxiolytic buspirone has been reported ineffective in suppressing withdrawal symptoms, particularly in long-term BZD users (253, 254). Hydroxyzine has also been found beneficial in treating patients for lorazepam withdrawal (255). 

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-... 

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. 

Anxiolytics with little abuse potential, such as buspirone, and antidepressants that have a benign side-effect profile and may reduce ethanol intake warrant careful evaluation in the treatment of anxious and depressed alcoholic patients. 

Ciraulo DA, Sands BE, Shader RI Critical review of liability for benzodiazepine abuse among alcoholics. Am J Psychiatry 145 1501-1506, 1988b Ciraulo DA, Barnhill JG, Ciraulo AM, et al Parental alcoholism as a risk factor in benzodiazepine abuse a pilot smdy. Am J Psychiatry 146 1333-1335, 1989 Ciraulo DA, Antal EJ, Smith RB, et al The relationship of alprazolam dose to steady-state plasma concentrations. J Clin Psychopharmacol 10 27—32, 1990 Ciraulo DA, Sarid-Segal O, Knapp C, et al Liability to alprazolam abuse in daughters of alcoholics. Am J Psychiatry 153 956-958, 1996 Ciraulo DA, Barnhill JG, Ciraulo AM, et al Alterations in pharmacodynamics of anxiolytics in abstinent alcoholic men subjective responses, abuse liability, and electroencephalographic effects of alprazolam, diazepam, and buspirone. J Clin Pharmacol 37 64-73, 1997... 

Dourish, CT, Hutson, PH and Curzon, G (1986) Putative anxiolytics 8-OHDPAT buspirone and TVXQ 7821 are agonists at 5-HTia autoreceptors in the raphe nuclei. Trends Pharmacol. Sci. 1 212-214. 

Alternative pharmacological approaches Clonidine, an o2 adrenergic agonist, has been employed as adjunctive therapy to assist in smoking cessation. However, results have been mixed or the effects small (Gourlay et al. 1994 Hilleman et al. 1993 Franks et al. 1989). Buspirone (BuSpar) is a 5-HTlA partial agonist with anxiolytic effects. It has been tested as a treatment for smoking cessation because anxiety is a prominent feature of nicotine withdrawal (Farid and Abate 1998). To date, results have been mixed and more controlled research is needed. 

Azapirones. Though several azapirones have been developed and tested in the laboratory setting, only one, bnspirone (Bnspar), is currently on the market. Buspirone is the first nonsedating, nonbenzodiazepine anxiolytic, other than the antidepressants described earlier. It has no dependence or addictive liability and is not lethal in overdose. Buspirone is also devoid of many of the problems of the benzodiazepines such as sedation, motor impairment, addiction, physical dependence, or withdrawal. Yet, doubts remain in the minds of many practitioners regarding the effectiveness of buspirone. This will be discussed in more detail later in this chapter. 

Anxiolytics clonazepam, diazepam, temazepam, triazolam, alprazolam, midazolam, buspirone Anticonvulsants ethosuximide, carbamazepine Calcium channel blockers diltiazem, felodipine, nifedipine, verapamil... 

Hippocampus, septum, amygdala, cortical limbic area Agonists buspirone, gepirone, ipsapirone, flesinoxan Antagonists WAY 100135, BMY7378, NAN-190 Possible clinical use of agonists anxiolytics, antidepressants 5-HTi receptors... 

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

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. 

Monitoring Effectiveness for more than 3 to 4 weeks has not been demonstrated in controlled trials. However, patients have been treated for a year without ill effect. If used for extended periods, periodically reassess the usefulness of the drug. interference with cognitive and motor performance Buspirone is less sedating than other anxiolytics and does not produce significant functional impairment. However, its CNS effect may not be predictable. Therefore, caution patients about driving or using complex machinery until they are certain that buspirone does not affect them adversely. 

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