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)

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

Benzodiazepines have been prescribed for the treatment of Generalized Anxiety Disorder (GAD) for nearly three decades due to their proven anxiolytic efficacy, despite a considerable side effect and abuse liability profile. A new class of compounds, the azapirones, have been developed as an alternative to benzodiazepine treatment. Ipsapirone is a novel anxiolytic azapirone which has high specificity for the 5-HT1A receptor and which has the potential for offering certain advantages over buspirone. The present 5-week study investigated three doses of ipsapirone (2.5mg, 5.0mg and 7.5mg tid) versus placebo in 267 GAD outpatients. Efficacy was evaluated using the Hamilton Anxiety Rating Scale (HAM-A), Zung Anxiety Scale (Zung-A), and Clinical Global Impression (CGI). The study design consisted of a 1-week placebo run-in, a 4-week double-blind treatment period, and a 1-week placebo washout. The 5.0mg group demonstrated consistently superior improvement in all efficacy variables during the treatment period, with significant differences (p < 0.05) from placebo and, at times, the 2.5mg and 7.5mg groups. Incidence of adverse events, primarily dizziness, nausea, sedation, and asthenia, was found to be dose proportional, with significant increase in the 7.5mg group, which may account for the diminished effectiveness seen with this dose. Our results suggest that ipsapirone may represent a viable treatment for GAD.
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PMID:A phase II multicenter dose-finding, efficacy and safety trial of ipsapirone in outpatients with generalized anxiety disorder. 791 45

The chemistry, pharmacology, pharmacokinetics, and clinical efficacy of nefazodone hydrochloride, a new antidepressant, are described. Nefazodone enhances serotonin (5-hydroxytryptamine [5-HT]) synaptic transmission by acting as an antagonist at 5-HT2 receptors and by inhibiting the reuptake of 5-HT. These two mechanisms combined may enhance 5-HT1A-mediated transmission. In addition, nefazodone weakly inhibits the reuptake of norepinephrine. Nefazodone is a structural analogue of trazodone but is pharmacologically distinct. In placebo-controlled trials, nefazodone was as effective as imipramine for the treatment of major depression and produced clinical benefits in patients with depression-related anxiety and sleep disturbances. More than 2000 patients have received nefazodone in clinical trials. The most commonly reported adverse drug reactions (ADRs) are asthenia, somnolence, dry mouth, nausea, constipation, dizziness, lightheadedness, confusion, abnormal vision, and blurred vision. The incidence of sexual-dysfunction ADRs may be less than that reported for other antidepressants. Nefazodone does not inhibit rapid-eye movement sleep. Nefazodone, an inhibitor of the hepatic P-450 isoenzyme CYP3A4, may increase concentrations of drugs metabolized by this isoenzyme, such as terfenadine, astemizole, triazolam, alprazolam, and midazolam. Caution should be exercised in administering nefazodone hydrochloride with triazolobenzodiazepines, and coadministration with terfenadine or astemizole is contra-indicated. The dosage should start at 100 mg twice daily and then be increased, depending on occurrence of ADRs and the patient's clinical response, to 300-600 mg daily. In elderly or debilitated patients, the initial dosage should be half the usual dosage. Nefazodone hydrochloride is as effective as other available antidepressants and may cause fewer ADRs.
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PMID:Nefazodone: a new antidepressant. 889 78