Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To explore 5-HT1A receptor responsivity in panic disorder (PD), hypothermic, neuroendocrine and behavioral responses to the selective partial 5-HT1A receptor agonist ipsapirone (IPS) were investigated in patients with primary PD and healthy controls. Fourteen patients and matched controls received a single oral dose of 0.3 mg/kg IPS or placebo under double-blind, random-assignment conditions. IPS induced hypothermia and corticotropin (ACTH)/cortisol release but had only minimal effects on behavior. Compared with controls, the patients with PD exhibited significantly attenuated thermoregulatory and neuroendocrine responses to IPS. Although the healthy subjects reported increased drowsiness and the PD patients rated themselves more nervous and less calm following administration of IPS, no consistent changes in ratings of anxiety or panic symptoms were recorded. The impaired hypothermic and ACTH/cortisol responses following 5-HT1A receptor activation reflects subsensitivity of both the pre- and post-synaptic 5-HT1A receptor-effector system, thus supporting the hypothesis that a 5-HT1A receptor-related serotonergic dysfunction may be linked to the pathophysiology of PD. Future studies of 5-HT1A receptor-effector complex function in conjunction with assessment of the responsivity of other subtypes (e.g. 5-HT2, 5-HT3) should promote the evaluation of 5-HT system integrity in anxiety disorders and its involvement in anxiolytic drug effects.
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PMID:5-HT1A receptor-effector system responsivity in panic disorder. 134 19

1. Azapirones, selective partial agonists at the 5-HT1A receptor subtype, induce hypothermia and corticotropin (ACTH)/cortisol release as specific functional correlates of central 5-HT1A receptor activation. 2. Compared to controls, hypothermic and ACTH/cortisol responses to the azapirone ipsapirone are attenuated in patients with unipolar depression and panic disorder but not in patients with obsessive-compulsive disorder. The impaired thermic and neuroendocrine responses are associated with increased basal cortisol secretion in depressed patients but not in patients with panic disorder. 3. Chronic treatment with the selective 5-HT reuptake inhibitor fluoxetine decreases 5-HT1A receptor-mediated responses in patients with obsessive-compulsive disorder, while long-term treatment with the tricyclic antidepressant amitriptyline further decreases hypothermia following ipsapirone but has no effect on ACTH/cortisol release. 4. Alteration of the 5-HT1A receptor and/or its signal transduction pathways may play a role in the pathophysiology and treatment of anxiety disorders and depression.
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PMID:5-HT1A receptor responsivity in anxiety disorders and depression. 176 90

Recent literature has addressed a frequent comorbidity between alcoholism and anxiety/depression. These disorders have been interdigitated with the brain amines serotonin (5-HT) and norepinephrine. We investigated 51 dually diagnosed patients (generalized anxiety disorder with depressive features plus alcohol abuse/dependency) under a randomized, double-blind, placebo-controlled trial employing the 5-HT1A compound buspirone. Buspirone was superior to placebo as an anxiolytic. It was well tolerated and reduced the number of days patients desired alcohol. At the final study dose, the buspirone metabolite 1-pyrimidinylpiperazine (1-PP) was significantly related to improvement in anxiety, global depressive symptoms, and number of days not using alcohol. Analysis using the Hamilton Rating Scale for Depression and its retardation cluster revealed significant improvement secondary to anxiolysis. Thus, buspirone (especially via its 1-PP metabolite) may be an effective treatment strategy in the anxious or mixed anxious-depressive patient with comorbid alcoholism when other conventional anxiolytics may be contraindicated.
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PMID:The association of buspirone and its metabolite 1-pyrimidinylpiperazine in the remission of comorbid anxiety with depressive features and alcohol dependency. 192 64

Ipsapirone is an azopirone derivative that selectively interacts with serotonin-1A (5-HT1A) receptors and fails to affect other neurotransmitter receptors. In this study, ipsapirone at 15 mg or 30 mg was compared with diazepam at 15 mg and placebo in a double-blind, random assignment study design in patients with generalized anxiety disorder (GAD). During 4 weeks of treatment, both active drugs were therapeutically superior to placebo, without significant drug vs. drug therapeutic differences. The side-effect profile of ipsapirone at 15 mg was favorable compared to diazepam, but at 30 mg ipsapirone produced significant gastrointestinal disturbances.
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PMID:Efficacy and safety of a putative anxiolytic agent: ipsapirone. 197 71

Buspirone, an azapirone derivative and a 5-HT1A partial agonist, is the first nonbenzodiazepine anxiolytic introduced into medicine for the treatment of generalized anxiety disorder. A series of well-controlled clinical trials demonstrated that its anxiolytic properties were similar to those of various benzodiazepines and significantly better than placebo. More recently, antidepressant effects were also observed. Patients with clinical indications for which buspirone seems to be particularly appropriate are those with generalized anxiety disorder, those with chronic anxiety, the anxious elderly, and, perhaps, many patients of all ages who suffer from mixed symptoms of anxiety and depression. Studies conducted with patients suffering from panic disorder have so far been inconclusive, and thus buspirone is, for the present at least, not recommended for routine treatment of panic disorder. Buspirone seems to be most helpful in anxious patients who do not demand immediate gratification or the immediate relief they associate with the benzodiazepine response. Slower and more gradual onset of anxiety relief is balanced by the increased safety and lack of dependency-producing aspects of buspirone. Finally, whether or not buspirone may possess "curative" properties, in addition to "anxiety-suppressant" properties, that allow the patient to improve coping skills with time requires further exploration.
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PMID:Buspirone in clinical practice. 221 69

In examining anxiety and the response of animal models to serotonergic drugs, four aspects should be taken into account: (1) the serotonin receptor is subdivided into at least six receptor subtypes; (2) benzodiazepines have acute anxiety-relieving effects, whereas antidepressants, serotonin-uptake inhibitors, buspirone, and serotonin antagonists have antianxiety effects only after prolonged administration; (3) diagnostic criteria differentiate several distinguishable anxiety disorders that have different responsiveness to serotonin-related drugs, and (4) various types of animal models exist, each responding differently to serotonin-related drugs. Perhaps particular animal models are relevant only for the study of one particular type of anxiety disorder. This differentiated view will be used when discussing the role of 5-hydroxytryptamine (5-HT) receptor subtypes in anxiety disorders and anxiety models. The 5-HT1A receptor is implicated in anxiety by the compounds buspirone and 8-hydroxy-2-(di-n-propyl-aminotetraline) (OHDPAT). The 5-HT1B or the 5-HT1D receptors play a role in the 'defensive burying' anxiety model and probably mediate antidepressant and antianxiety effects of serotonin-uptake inhibitors. The 5-HT1C receptor plays a role in the aversive brain stimulation anxiety model and could play a role in antianxiety effects of mianserin. The 5-HT2 receptor is selectively blocked by ritanserin. In animal 'conflict models' for anxiety, 5-HT-2-receptor antagonists are active, although they are weaker than the benzodiazepines. The 5-HT3-receptor antagonists are reported to be active in social interaction models for anxiety; however, clinical experience in anxiety using these compounds is not yet available.
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PMID:Animal models for anxiety and response to serotonergic drugs. 256 38

Certain evidence suggests that buspirone, a novel nonbenzodiazepine anxiolytic, may be a 5-HT1A serotonergic agonist and may antagonize postsynaptic dopaminergic receptors. The latter property raises questions regarding a dyskinesia- or extrapyramidal symptom-inducing potential. We monitored serum prolactin and growth hormone in 10 subjects with generalized anxiety disorder and 10 matched controls before and after 4 weeks of pharmacotherapy. A drug effect upon serotonin-modulated prolactin release or on the tubero-infundibular dopamine axis (prolactin; growth hormone) was negligible at clinically effective dosages of buspirone. Concomitant buspirone levels also failed to demonstrate any significant relationships.
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PMID:Buspirone: effects on prolactin and growth hormone as a function of drug level in generalized anxiety. 272 31

Anxiety has historically been treated by agents with a sedative component to their action. In the last decade or so it has been determined that gamma-aminobutyric acid (GABA) receptors may mediate the anxiolytic actions of the benzodiazepines, propanediol carbamates, barbiturates, and ethanol. However, inasmuch as these drugs have additional pharmacological properties (sedation, muscle relaxation, seizure control), the search for an anxioselective drug was continued. Buspirone appears to be such a drug. Clinical studies have clearly demonstrated the efficacy of buspirone in the treatment of generalized anxiety disorder without the ancillary pharmacology of earlier anxiolytics. Buspirone does not act on the GABA receptor. Rather, its most salient interaction with neurotransmitter receptors occurs at the 5-HT1A serotonin receptor. This action is supported by studies focused on receptor binding, anatomical localization, biochemistry, neurophysiology, and animal behavior. The recognition that action at 5-HT1A receptors may be a viable approach to the pharmacotherapy of anxiety is evidenced by the number of other agents of this class under development by a number of pharmaceutical companies.
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PMID:Buspirone, a new approach to the treatment of anxiety. 283 52

Although many serotonin (5-hydroxytryptamine; 5-HT) receptors have been identified, our knowledge of many of the subtypes is limited. However, we do know that 5-HT1A agonists are involved in the treatment of certain anxiety disorders, that 5-HT1C and 5-HT2 receptor antagonists may be indicated for the treatment of generalized anxiety disorder, and that 5-HT1D receptor agonists are used in the treatment of migraine. Recent research has identified that various abnormalities in serotonergic function are involved in the pathogenesis of depression and anxiety, and has facilitated the development of new pharmacological agents with great therapeutic potential, for example the selective serotonin reuptake inhibitors (SSRIs). These agents appear to be effective in the treatment of many anxiety states and may have greater efficacy than other agents in the treatment of certain affective disorders. As the central serotonergic system continues to be "mapped", newer and more selective drugs are likely to be introduced, thereby possibly improving the overall successful management of depression and anxiety disorders.
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PMID:The role of serotonin in depression and anxiety. 762 23

Ipsapirone is a partial 5-HT1A agonist which appears promising for the pharmacologic treatment of anxiety. In this four-week, double-blind, 19-center study, 249 outpatients with generalized anxiety disorder were randomized to one of four treatments: ipsapirone, 5 or 10 mg t.i.d., diazepam 5 mg t.i.d., or placebo. Both active treatments were significantly superior to placebo in reducing anxiety symptoms, although response to ipsapirone was not significant until week 2 while diazepam had a more rapid onset. Five mg t.i.d. was the optimal ipsapirone dose. At 10 mg t.i.d. adverse experiences prompted more patients to discontinue treatment. Adverse experiences that were reported significantly more often for ipsapirone than placebo included asthenia, nausea, dizziness, paresthesias and sweating. Sedation was the most common diazepam-related side effect. The results of this study when combined with others suggest that 5 mg t.i.d. of ipsapirone is an effective and well-tolerated anxiolytic without many of the risks of benzodiazepine therapy. Dosage escalation by patients is unlikely because of an increased risk of side effects.
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PMID:A placebo-controlled double-blind multicenter trial of two doses of ipsapirone versus diazepam in generalized anxiety disorder. 790 26


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