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)

Buspirone (Buspar) is a azaspirodecanedione anxiolytic agent. Its mechanism of action is extremely complex, but current investigations indicate that its main neuropharmacologic effects are mediated by the 5-HT1A receptors. Other neuroreceptor systems could be involved, as buspirone displays some affinity for DA2 autoreceptors and 5-HT2 receptors. It has been proposed that inhibition of synthesis and release of serotonin result through the combined interactions of neuroreceptors and secondary messenger systems. This action leads to inhibition of the firing rate of 5-HT-containing neurons in the dorsal raphe. From this novel profile, that differs from that of the benzodiazepines, buspirone lacks anticonvulsant and muscle-relaxant properties, and causes only minimal sedation. The drug is rapidly absorbed after oral administration, with a mean bioavailability of 3.9%. After a single oral dose, the mean elimination half-life is 2.1 hours. Buspirone is mainly bound to albumin and alpha 1-acid glycoprotein. It is metabolized to an active metabolite 1-(2-pyrimidinyl) piperazine (1-PP). The mean elimination half-life of 1-PP is 6.1 hours. Buspirone is indicated in the treatment of generalized anxiety disorders. Its efficacy is comparable to the benzodiazepines. Its use in depression and panic disorders requires further investigation. When combined with alcohol or given alone, psychomotor impairment was not detected. Abuse, dependence, and withdrawal symptoms have not been reported. The frequency of adverse effects is low, and the most common effects are headaches, dizziness, nervousness, and lightheadness. Buspirone should be added to drug formularies and could represent a significant addition in psychopharmacology.
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PMID:Buspirone: an update on a unique anxiolytic agent. 304 84

High-pressure neurological syndrome (HPNS) is a condition encountered in diving beyond a depth of 100 m. Manifestations include headache, tremor, myoclonus, neuropsychiatric disturbances and EEG changes. Convulsions are seen only in experimental animals. Most of the changes are reversible on surfacing but some such as memory disturbances may linger on for long periods. Excessive atmospheric pressure is the most important factor in the pathogenesis of HPNS. Neurotransmitter changes occur of which serotonin appears to be a more likely mediator because of the resemblance of HPNS to serotonin syndrome. Anesthetics and anticonvulsants have been used in experimental animals but are unsuitable for use in human divers. Breathing gas mixtures such as heliox have enabled the extension of depth of diving without HPNS. Use of 5-HT1A receptor antagonists may provide an interesting approach to prevention of HPNS.
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PMID:High-pressure neurological syndrome (HPNS). 794 56

Flesinoxan, a full 5-HT1A receptor agonist, was administered (4-8 mg) to treatment-resistant depressed patients in an open study. Safety and tolerance of the substance appeared satisfactory. Headache, dizziness and nausea were the most frequently reported side effects. The observations suggested that flesinoxan is an antidepressant agent and that it may be of particular value in some difficult, treatment-resistant depressions. Based on these observations, a double-blind, placebo-controlled evaluation of flesinoxan's efficacy appears warranted.
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PMID:An open study of oral flesinoxan, a 5-HT1A receptor agonist, in treatment-resistant depression. 826 14

The ergot alkaloids are a family of chemical entities that have many pharmacologic effects. Their diversity results from their interaction with multiple receptors, their variable receptor affinity and intrinsic activity, and their variable organ-specific receptor access. Ergotamine tartrate (ET) was one of the first ergot alkaloids to be isolated. Dihydroergotamine (DHE) is synthesized by reducing an unsaturated bond in ergotamine (E); this modification results in a changed pharmacologic profile. Dihydroergotamine exhibits greater alpha-adrenergic antagonist activity and much less potent arterial vasoconstriction and emetic potential. Both E and DHE are 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT1F receptor agonists. The vasoconstrictor activities of these ergot compounds have long been believed to be the basis of their clinical effects, but recent evidence suggests that their antimigraine action may result in part from their inhibitory effects on neurogenic inflammation and neuronal transmission and not from vasoconstriction. Improvements in assay methodology have provided more accurate determination of the pharmacokinetics of E and DHE. The long duration of action appears to result from active metabolites and tight tissue binding. Intranasal (IN) administration of DHE delivers adequate plasma concentrations of the drug without the need for parenteral administration and should further expand its role in migraine pharmacotherapy.
Headache 1997
PMID:The pharmacology of ergotamine and dihydroergotamine. 900 70

Ipsapirone, an azapirone with 5-hydroxytryptamine (5-HT1A) partial agonist activity, has been shown in preliminary studies to be effective in the treatment of major depressive disorder. This 8-week, randomized, double-blind study compared the efficacy, safety, and tolerability of three fixed doses of controlled-release ipsapirone (10-, 30-, and 50-mg dose once daily) with placebo in 410 patients with moderate to severe major depression (Hamilton Rating Scale for Depression [HAM-D] score > or = 20). The 10-mg ipsapirone treatment arm was discontinued early in the study. A total of 390 patients were eligible for evaluation in the intent-to-treat sample. The primary efficacy variable was the change in HAM-D total score from baseline to visit 8. There was no significant difference in efficacy in the two treatment groups versus the placebo group. The overall treatment response, defined as a 50% decrease in the HAM-D total score from baseline, was 43% with ipsapirone 50 mg given once daily, 34% with ipsapirone 30 mg given once daily, and 35% with placebo. In subanalyses, ipsapirone 50 mg given once daily was superior to placebo according to the HAM-D Core Depression (mood, guilt, interest, psychomotor activity) subtotal (p = 0.0453) and Melancholic item (p = 0.0225). Ipsapirone 30 mg given once daily was superior to placebo only in patients with moderate depression (baseline HAM-D total score < or = 25; p = 0.0100). The most common adverse effect in all groups was headache. The only dose-dependent adverse effects were dizziness and nausea.
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PMID:A Canadian multicenter study of three fixed doses of controlled-release ipsapirone in outpatients with moderate to severe major depression. 969 Jun 91

Buspirone is an azapirone with 5-HT1A partial agonist activity which has demonstrated efficacy in the treatment of generalized anxiety disorder, commonly referred to as persistent anxiety. In this meta-analysis report, safety results from two studies comparing buspirone 15 mg twice daily (BID) with buspirone 10 mg three times daily (TID) in patients with persistent anxiety are presented. In the study protocols, qualified patients completed a 7-day placebo lead-in phase and were randomized to receive buspirone 30 mg per day, as either a BID or TID regimen, for 6-8 weeks. A total of 289 patients received buspirone 15 mg BID (n = 144) or 10 mg TID (n = 145) at 15 sites. The incidence of adverse events was similar between the two treatment groups, except for a significantly greater incidence of palpitations in patients receiving buspirone BID (5%) compared to buspirone TID (1%). The most frequently reported adverse events for both buspirone BID- and TID-treated patients were dizziness, headache, and nausea. No appreciable differences between treatments were observed for vital signs, physical exam, ECG, or clinical laboratory results. A change to BID dosing for buspirone may offer convenience and possibly higher compliance in patients with persistent anxiety without compromising the excellent safety and tolerability profile of the medication.
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PMID:Meta-analysis of the safety and tolerability of two dose regimens of buspirone in patients with persistent anxiety. 1035 51

Serotonin has long been implicated as a key neurotransmitter in migraine. There is a dearth of research specifically examining 5-HT1A receptor sensitivity in migraine despite the importance of this receptor in regulating central serotonergic tone. In this study we examined the hypothesis that migraine without aura is associated with hypersensitivity of central 5-HT1A receptors, using a 5-HT1A neuroendocrine challenge drug and comparing serum prolactin responses between a test group with migraine and a matched group of healthy controls. Twelve female subjects fulfilling International Headache Society (IHS) criteria for migraine without aura were evaluated. Following an overnight fast, subjects presented for testing at 9am. An intravenous canula was inserted and serum prolactin was assessed at baseline and every 30 min for 3 h following a single dose of 30 mg oral buspirone, a 5-HT1A-receptor agonist. Subjects were assessed during the first 5 days of the menstrual cycle. No subjects were taking psychotropic medication or migraine prophylactic treatment. Patients with current or previous psychiatric disorder, daily headache or analgesic overuse were excluded. 16 healthy female volunteers matched for age and menstrual status were also evaluated and served as controls. There was no difference in baseline prolactin between groups. There was a significant rise in prolactin following buspirone in both groups. Subjects with migraine had a significantly increased prolactin response to buspirone (delta max) compared to controls (P < 0.001). This study supports the hypothesis that migraine without aura is associated with a relative hypersensitivity of central 5-HT1A receptors. This is of relevance given the role of the 5-HT1A receptor in controlling raphe 5-HT tone and in the possible association between migraine and anxiety and depression.
Cephalalgia 2003 Feb
PMID:Central 5-HT receptor hypersensitivity in migraine without aura. 1515 63

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of aripiprazole are discussed. Aripiprazole is a third-generation antipsychotic agent indicated for use in the treatment of schizophrenia. Unlike other antipsychotics, aripiprazole demonstrates mixed D2 and serotonin (5-HT1A) receptor agonist-antagonist activity that is hypothesized to improve schlzophrenia's positive and negative symptoms; the drug has been referred to as a dopamine-serotonin stabilizer. Aripiprazole is well absorbed, with peak plasma concentrations occurring within three to five hours after administration. The oral availability is 87%. The mean elimination half-life is about 75 hours for aripiprazole and 94 hours for its active metabolite. In controlled, randomized, multicenter trials, aripiprazole has demonstrated efficacy in the treatment of schizophrenia comparable to that of haloperidol and superior to placebo. In a single clinical trial, aripiprazole was superior to placebo in the treatment of acute mania. The most frequent adverse effects are headache, anxiety, insomnia, nausea, vomiting, and lightheadedness. Because aripiprazole is a substrate of both cytochrome P-450 isoenzymes 3A4 and 2D6, there is a potential for other drugs to affect its metabolism. The recommended starting dosage is 10 or 15 mg daily, preferably administered with meals. Aripiprazole offers an alternative to second-generation antipsychotic agents in the treatment of schizophrenia.
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PMID:Aripiprazole. 1468 20

The triptans are agonists at serotonin (5-HT)1B/1D receptors; however, they are also active at 5-HT1A and 5-HT1F receptors. We conducted this series of experiments to further elucidate the site of action of naratriptan using a well-established animal model of trigeminovascular stimulation. Following electrical stimulation of the superior sagittal sinus of the cat, single cell responses (n=83) were recorded in the trigeminal nucleus caudalis. Most cells (91%) also responded to electrical and mechanical stimulation of cutaneous or mucosal facial receptive fields. The microiontophoretic application of naratriptan resulted in a significant suppression of the response to sagittal sinus stimulation (response suppressed by 47 +/- 4%, P<0.001). The effect of naratriptan was significantly attenuated by application of either the 5-HT(1B/1D) receptor antagonist GR-127935 (P<0.001) or the 5-HT1A antagonist WAY-100635 (P<0.05). The response of single cells to receptive field stimulation was also suppressed by microiontophoretic application of naratriptan, but by only 20 +/- 3%. Intravenous administration of naratriptan resulted in a similar selective suppression of sagittal sinus vs. receptive field responses in trigeminal neurones. These results indicate that naratriptan has a central effect in the trigeminovascular system, selectively inhibiting afferent activity in craniovascular neurones, via both 5-HT(1B/1D) and 5-HT1A receptors.
Cephalalgia 2004 Feb
PMID:Naratriptan has a selective inhibitory effect on trigeminovascular neurones at central 5-HT1A and 5-HT(1B/1D) receptors in the cat: implications for migraine therapy. 1472 5

To evaluate long-term efficacy and tolerability of the serotonin 5-HT1A receptor agonist, gepirone extended release (ER), a multicenter, randomized, placebo-controlled relapse prevention study was performed in patients with recurrent major depression (DSM-IV criteria). Patients 18 to 70 years, with a primary diagnosis of recurrent major depression (DSM-IV; 296.3) and a screening and baseline HAMD-17 total score >/=20 were eligible. After a 3- to 14-day (dependent on pretrial medication) single-blind placebo washout period, eligible patients entered an 8- or 12-week (depending on time to remission) open-label gepirone ER treatment period. They initially received a dose of 20 mg/d gepirone ER and were titrated to a dose of 40 to 80 mg/d. Patients who achieved remission (HAMD-17 total score </=8) were randomized to double-blind continuation of their gepirone ER treatment or placebo for 40 to 44 weeks. The primary end point was a comparison of the relapse rates between gepirone ER and placebo. Relapse was defined as a HAMD-17 total score >/=16 or discontinuation for lack of efficacy. A total of 420 patients were treated in the open-label phase. Of these, 303 (72.1%) completed the open-label phase and 250 (59.5%) fulfilled the criteria for remission and were randomized into the double-blind continuation phase (gepirone ER: n = 126; placebo: n = 124). The mean (+/-SD) final titrated dose of gepirone ER was 61.9 (+/-17.0) mg/d in the double-blind continuation phase. The relapse rate in the gepirone ER group was statistically significantly lower than that in the placebo group, 23.0% versus 34.7%, respectively (P = 0.024). During the open-label phase, adverse events that occurred in more than 5% of patients were nausea (15.7%), dizziness (13.1%), headache (12.9%), insomnia (6.2%), and vertigo (6.0%). During the continuation phase, the incidence of newly or re-emerging adverse events was similar with gepirone ER (43.7%) and placebo (42.7%). Adverse events different from those occurring during the open-label phase were not apparent. All adverse events occurred in less than 5% of patients with the exception of flu syndrome and headache. In conclusion, gepirone ER at a dose range of 40 to 80 mg/d is effective for relapse prevention in patients with recurrent major depression. It is well tolerated during long-term treatment for up to approximately one year.
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PMID:Relapse prevention with gepirone ER in outpatients with major depression. 1564 3


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