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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical trials have demonstrated that buspirone (BuSpar) is effective in the treatment of anxiety with efficacy and dosage comparable to diazepam or chlorazepate. Buspirone has a unique structure and a pharmacologic profile which distinguishes it from the benzodiazepines. Because it lacks the anticonvulsant, sedative, and muscle-relaxant properties associated with other anxiolytics, buspirone has been termed "anxioselective." Animal studies suggest that it lacks potential for abuse, and this finding is supported by clinical investigations. Further preclinical work supports the contention that buspirone lacks liability to produce physical dependence or to significantly interact with central nervous system depressants such as ethanol. Moreover, biochemical investigations have not identified any direct interaction of buspirone with the benzodiazepine-gamma-aminobutyric acid-chloride ionophore complex. Pharmacologic studies on the molecular level indicate that buspirone interacts with dopamine and serotonin receptors. Recent behavioral, electrophysiological, and biochemical studies have clearly demonstrated that early hypotheses that buspirone might be considered a neuroleptic are no longer tenable. Recent evidence indicates that other neurotransmitter systems (serotonin, norepinephrine, acetylcholine) mediate buspirone's effects. It is hoped that future studies can define the mechanism by which buspirone alleviates the clinical manifestations of anxiety.
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PMID:Pharmacological and clinical effects of buspirone. 286 49

Buspirone is a novel anxiolytic agent unrelated to the benzodiazepines in structure or pharmacologic properties. Extensive clinical studies have shown buspirone to be effective in the treatment of anxiety, with efficacy comparable to diazepam or clorazepate. Buspirone exhibits a unique pharmacologic profile in that it alleviates anxiety without causing sedation or functional impairment and does not promote abuse or physical dependence. 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. Biochemical and electrophysiologic studies indicate that buspirone alters monoaminergic and GABAergic systems in a manner different from that of the benzodiazepines. The uniform depressant action of the benzodiazepines upon serotonergic, noradrenergic, and dopaminergic cell firing may result from their facilitatory effect on gamma-aminobutyric acid and its known inhibitory influence in these monoaminergic areas. Unlike the benzodiazepines, buspirone exerts a differential influence upon monoaminergic neuronal activity, suppressing serotonergic activity while enhancing dopaminergic and noradrenergic cell firing. The mechanism of action of buspirone challenges the notion that only one neurotransmitter mediates anxiety. The interaction with multiple neurotransmitters at multiple brain sites suggests that buspirone may alter diverse activities within a "neural matrix of anxiety." In contrast to the benzodiazepines, buspirone orchestrates activity within this neural matrix to achieve effective treatment of anxiety while preserving arousal and attentional processes.
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PMID:Buspirone: review of its pharmacology and current perspectives on its mechanism of action. 287 Jun 39

Although short-term therapy for patients with anxiety disorders has been the accepted mode of therapy, it has become increasingly evident that certain patients with generalized anxiety disorder, panic disorder, and chronic illness may require longer-term therapy. Therapeutic goals for such patients include reducing anxiety symptoms, returning the patient to normal or near-normal functioning, and improving quality of life. Clinicians must choose the appropriate drug regimen with regard to duration, continuous versus intermittent treatment, and administration on a daily versus as-needed basis. Because of the nature of some anxiety disorders, intermittent therapy very often may be preferred. Benzodiazepines are highly effective and safe anxiolytics, but with continuous use these agents have demonstrated psychologic and physical dependence problems. Other agents, such as tricyclic antidepressants and monoamine oxidase inhibitors, also relieve anxiety, although they have been shown to be unsuited for indiscriminate use. Buspirone, a newer anxiolytic, seems to be both effective and without abuse or dependence potential. In all cases, the prudent clinician should combine good patient management within the context of a good doctor-patient relationship.
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PMID:Antianxiety therapy: potential value of long-term treatment. 289 88

Clinical trials have indicated that buspirone (Buspar) is effective in the treatment of anxiety with efficacy and dosage comparable to diazepam. Until recently it has been thought that antianxiety drugs must alter benzodiazepine receptor binding in vitro. However, buspirone lacks any structural similarity to te benzodiazepines and does not interact with the benzodiazepine/gamma-aminobutyric acid (GABA) axis. Specifically, buspirone neither stimulates nor inhibits [3H]benzodiazepine binding, does not affect the influence o GABA or halide anions on benzodiazepine binding, and does not interfere with GABA binding or uptake. Behavioral testing has revealed that buspirone does not produce muscle weakness, does not control seizures, does not potentiate the impairment of psychophysiological function or lethality produced by administration of CNS depressants, does not produce sedation/hypnosis and does not appear to possess any abuse potential or liability for physical dependence. Thus, buspirone has been termed an anxioselective agent. Buspirone appears to only interact with the dopaminergic system with reasonable potency and exhibits properties of both a dopamine agonist and a dopamine antagonist. This suggests that dopamine is implicated in the etiology and expression of anxiety. A discussion of this implication is presented with a review of the clinical efficacy of nonbenzodiazepine drugs, especially dopamine agonists and dopamine antagonists, in the management of anxiety. In addition, neuropharmacological studies which have investigated the role of dopamine in animal models of anxiety are considered. Finally, the multiplicity of dopamine receptors and their regional localization in the brain are considered in the formulation of an hypothesis which features a role for the dopaminergic agents in the pharmacotherapy of anxiety.
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PMID:Dopamine and antianxiety activity. 613 25

Buspirone is a clinically effective anxiolytic with a unique structure and pharmacology which distinguishes it from the benzodiazepines. It has been termed anxioselective because it lacks anticonvulsant, sedative, or muscle-relaxant properties. Preclinical evidence suggests it lacks potential for abuse or physical dependence and interacts minimally with CNS depressants such as alcohol. Rather than working through traditional benzodiazepine mechanisms, buspirone affects diverse aspects of the brain's neurochemical circuitry. For example, it exerts potent influences on the nigrostriatal and mesolimbic dopamine systems, the dorsal raphe serotonergic system, and the locus coeruleus noradrenergic system. Although without direct receptor interaction, potentiation of cholinergically mediated behavior and involvement with GABAergic neurotransmission have also been demonstrated.
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PMID:Neuropharmacology of buspirone. 615 May 10

Buspirone HCl (Buspar) is a novel anxiolytic agent unrelated to the benzodiazepines or other psychotherapeutic agents. Animal studies support an anxioselective profile, i.e. relief of anxiety without sedation, muscle relaxation or anticonvulsant activity. Double-blind clinical studies show buspirone to be effective in the treatment of anxiety and anxiety in the presence of depression. The effects of buspirone on psychomotor function, physical dependence and abuse potential tests are similar to those seen with placebo treatments. Mechanism of action studies indicate activity in a variety of neuronal systems.
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PMID:Buspirone: an anxioselective alternative for the management of anxiety disorders. 636 36

Generalized Anxiety Disorder (GAD) is a highly prevalent condition whose course of illness is often chronic in nature and fluctuating in severity. Pharmacotherapy options include the benzodiazepines, the azapirones, of which only buspirone is marketed at the present time, and the antidepressant imipramine. Buspirone is probably the treatment of choice when prolonged therapy is indicated because it does not produce physical dependence, dose not interact with alcohol, and does not cause psychomotor impairment. Dosing instructions for buspirone and guidelines for switching patients from benzodiazepines to buspirone are offered. Non-drug therapies such as interpersonal and cognitive therapies are often also found helpful in treating patients with GAD.
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PMID:Strategies for treatment of generalized anxiety in the primary care setting. 1156 43

Less than one third of people afflicted with generalized anxiety disorder (GAD) experience spontaneous remission, and the symptoms of GAD wax and wane throughout a person's life. The burden of GAD may be reduced with psychopharmacologic therapy. The medications with the most evidence of efficacy in GAD are the benzodiazepines, including a new long-acting formulation of alprazolam. These drugs have a low incidence of side effects but may cause physical dependence, withdrawal, and sedation. Antidepressants are also efficacious in GAD but act less quickly than benzodiazepines. Tricyclic antidepressants such as imipramine may substantially reduce symptoms of anxiety but are not considered a first-line therapy because of their side effects spectrum. The extended-release formulation of venlafaxine and selective serotonin reuptake inhibitors such as paroxetine and sertraline are also efficacious in GAD. While their association with sexual dysfunction may be intolerable for some adults, these drugs may be more appropriate than the benzodiazepines because their chronic use does not lead to dependence. Buspirone also significantly reduces symptoms of GAD and is associated with less sexual dysfunction than SSRIs and less sedation than benzodiazepines. Combining antidepressant and benzodiazepine therapy or medication treatment and psychotherapy may lead to an increase in improvement in patients not responding to 1 treatment approach alone. The most effective treatment for managing the recurrent symptoms of this chronic disorder will remain unknown until more long-term studies using both drug and nondrug therapies are conducted. Remission rates are still only about 40%, signifying the need for improved treatment interventions.
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PMID:Pharmacotherapy of generalized anxiety disorder. 1256 13