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)

The effect of the 5-HT1A agonists ipsapirone (5 mg/kg), buspirone (5 mg/kg) and 8-OH-DPAT (0.5 mg/kg) on experimental anxiety was examined in sham-operated, adrenalectomized and adrenally demedullated male rats. The animal model of anxiety used was the defensive burying test. At the doses selected, all 5-HT1A compounds produced an anxiolytic-like action by reducing the burying behavior in both sham-operated and demedullated rats. However, in adrenalectomized subjects, while 8-OH-DPAT still reduced burying behavior, ipsapirone and buspirone lost their action. Data suggest that adrenocortical secretions play a role in the anxiolytic-like actions of buspirone and ipsapirone, but not in those of 8-OH-DPAT. Buspirone and ipsapirone also produced a reduction in burying behavior latency in sham-operated animals that was not observed in adrenalectomized or adrenally demedullated rats. These data suggest that adrenaline may be participating in the action of these compounds on the burying behavior latency. Present findings support possible direct relationships between the stimulation of 5-HT1A receptors and adrenal secretions.
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PMID:Blockade of the anxiolytic-like action of ipsapirone and buspirone, but not that of 8-OH-DPAT, by adrenalectomy in male rats. 1034 68

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

Buspirone, a 5-HT1A agonist, has been shown to decrease the intake of ethanol when given as a single dose to rats with a psychological dependence induced according to our rat model of alcoholism. The present experiment evaluates the effects different treatments with buspirone have on voluntary ethanol intake in these psychologically dependent rats. As a first treatment, buspirone was given once daily for 23 days at the dose of 20 mg/kg/day. Ethanol was withheld except for the first and the last day of the treatment. On the first day, the buspirone injection decreased ethanol intake from the pretreatment value (1.94+/-0.18 g/kg/day), down to 1.36+/-0.18 g/kg (p < 0.01, n = 12). The rats were again given a choice between water and 10% ethanol after the last injection of buspirone. During the following 24 hr period, the ethanol intake was increased to 3.56+/-0.24 g/kg/day (p < 0.001 vs. the pretreatment intake, n = 12). A loss of correlation with the pretreatment intake of ethanol indicated an altered regulation of ethanol intake for approximately 3 more weeks. Fifteen weeks after the start of the first treatment, buspirone (20 mg/kg) was re-tested as a single dose, with no effect on ethanol intake. Twenty-two weeks after the start of the first treatment, a 1-week treatment with 20 mg/kg/day of buspirone was started. During this treatment, the rats had a continuous choice between 10% ethanol and water. There was, as in the first re-test, no effect on ethanol intake on the first day of the treatment. However, on the last 2 days of the treatment, the ethanol intake was increased to 2.86+/-0.28 g/kg and to 2.89+/-0.26 g/kg respectively (p < 0.05, n = 10 on both days, compared with the pretreatment intake of 1.78+/-0.36 g/kg). Thus, an acute dose of buspirone can decrease voluntary ethanol intake in psychologically dependent rats, but long-lasting changes in the effect of buspirone seem to develop during a 3-week treatment period.
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PMID:Acute and long term effects of buspirone treatments on voluntary ethanol intake in a rat model of alcoholism. 1037 1

The effects of buspirone, fluvoxamine and diazepam were investigated, using healthy volunteers, in an aversive conditioning paradigm, a putative model for conditioned anxiety. The main prediction was that buspirone, an anxiolytic agent which reduces activity in serotonin (5-hydroxytryptophan, 5-HT) neurones, would attenuate aversively conditioned skin conductance responses. Skin conductance responses were recorded to 10 neutral tones (habituation phase). Tone 11 was immediately followed by a 1-s 90-dB aversive white noise (unconditioned stimulus). The conditioning trial reinstated responding to a second presentation of the tones (extinction phase). Skin conductance response amplitude, inter-response level and spontaneous fluctuations were recorded. There were five treatment groups comprising five men and five women. One control group took placebo, another control group received nothing; there was no effect of placebo on any measure. Diazepam (2 mg, p.o.), a positive comparator, markedly reduced the amplitude of skin conductance responses at all phases of the experiment, but only in women. Buspirone (5 mg, p.o.) had the predicted effect of accelerating extinction but also of unexpectedly accelerated habituation of skin conductance responses. There was a trend to reduce spontaneous fluctuations and no effect on skin conductance level. The effects of buspirone were thus specific to responses to stimuli. Fluvoxamine (25 mg, p.o.) had similar effects to buspirone and diazepam in women. An action common to buspirone, fluvoxamine and diazepam, which may account for their shared effect on conditioned autonomic responses, is the suppression of neural activity in the dorsal raphe nucleus. It is argued that enhanced habituation must involve a different mechanism, such as enhanced 5-HT1A function in the terminal fields of the median raphe nucleus.
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PMID:Comparison of buspirone with diazepam and fluvoxamine on aversive classical conditioning in humans. 1047 16

We have studied the effects of acute serotonin (5-HT) 5-HT1A receptor agonist buspirone (0.5, 1.0, 2.5 and 5.0 mg/kg, s.c.), gepirone (5.0 and 10 mg/kg, s.c.), and 8-OH-DPAT (0.1, 0.25, and 0.5 mg/kg, i.p.) treatment on the apomorphine-induced aggressive behaviour in adult male Wistar rats. Buspirone in doses of 2.5 and 5.0 mg/kg completely blocked, gepirone (10 mg/kg) significantly attenuated the aggressiveness, and 8-OH-DPAT abolished aggressive behaviour only in the lowest dose used (0.1 mg/kg) which effect disappeared in higher doses. The antiaggressive effect of buspirone (2.5 mg/kg) and gepirone (10 mg/kg) was not reversed by a 5-HT1A receptor antagonist WAY 100635 (0.3 mg/kg). All 5-HT1A receptor agonists tested dose-dependently decreased the exploratory behaviour of experimentally naive rats, while buspirone (2.5 mg/kg) and gepirone (10 mg/kg) had only a weak effect on the locomotor activity and stereotyped behaviour in the apomorphine-pre-sensitised rats. In conclusion, our experiments demonstrate the 5-HTIA receptors may be involved in the mediation of the apomorphine-induced aggressive behaviour in adult male Wistar rats. However, the prominent antiaggressive effect of buspirone, and to a lesser extent--gepirone, seems to be mediated by some other mechanisms, evidently via the dopamine D2 receptors.
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PMID:5-HT1A receptor agonists buspirone and gepirone attenuate apomorphine-induced aggressive behaviour in adult male Wistar rats. 1122 Apr 92

Previous reports indicate that the behavioural effects (including anxiolytic-like actions, hypothermia, "serotonergic syndrome," maternal behaviour and aggression and reduction in ambulation) of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), are completely blocked in lactating rats. The present study compares the behavioural effects of buspirone (1.25, 2.5 and 5.0 mg/kg) and diazepam (0.5, 1.0, 2.0 and 4.0 mg/kg) between ovariectomized and mid-lactating rats. The study was carried out on Wistar female rats under inverted light/dark cycle conditions, by using the burying behaviour paradigm, the elevated plus maze and a general activity test. In both ovariectomized and lactating rats, diazepam produced a dose-dependent reduction in burying behaviour and an increase in the time spent in open arms, responses interpreted as anxiolytic. Buspirone at all doses (1.25, 2.5 and 5.0 mg/kg) produced clear motor impairments in lactating, but not in ovariectomized animals, indicating that the effects of this drug on the anxiety paradigms are unspecific. Diazepam, by contrast, at the highest dose (4.0 mg/kg) similarly inhibited ambulation in both conditions. In the elevated plus maze, control lactating subjects spent more time in the open arms compared with saline-treated ovariectomized subjects, suggesting an anxiolytic-like effect of lactation per se. The present results support the idea that some behavioural actions of drugs acting at the serotonergic system vary between ovariectomized and lactating rats.
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PMID:Diazepam, but not buspirone, induces similar anxiolytic-like actions in lactating and ovariectomized Wistar rats. 1156 45

Buspirone (busp) a piperazinyl derivative with anxiolytic properties is a partial agonist on 5-HT1A with affinity for D2-like dopaminergic receptors (RD2). The objective of this study was to verify the effects of busp on RD2. Female Wistar rats 150-200 g were treated with busp (5 and 10 mg/kg, p.o.) 1 or 2 times daily for 7 days. Controls (C) received saline. The density of RD2 (fmol/mg protein) was determined through binding assays in striatum (ST) using [3H]-spiroperidol as radioligand. No alteration in Bmax or Kd values were seen after busp administration once a day. However, a RD2 upregulation of 55 % increase was observed after busp 2 times a day with no change in Kd values. The results showed that busp interact not only with serotonergic, but also with dopaminergic system.
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PMID:[Buspirone increases D2-like dopaminergic receptor density in rat corpus striatum]. 1196 7

The hypothermia produced by 5-HT1A agonists had initially been claimed to be caused by the activation of cell body 5-HT1A autoreceptors resulting in decreased 5-HT transmission in laboratory animals. In order to address this issue in humans, 12 healthy volunteers underwent a dietary tryptophan depletion paradigm to decrease 5-HT availability, under double-blind conditions, during which body temperature was monitored following oral administration of the 5-HT1A agonist buspirone (30 mg). In addition, plasma prolactin and growth hormone evaluations, two responses that are mediated via the direct activation of postsynaptic 5-HT1A receptors, were determined. The hypothesis was that if responses are mediated by decreased transmission at postsynaptic 5-HT1A receptors, resulting from dampened 5-HT release as a consequence of 5-HT1A autoreceptors activation, then responses to the exogenous 5-HT1A agonist should be attenuated when 5-HT availability has been markedly decreased beforehand. Buspirone produced the same significant increase in prolactin and growth hormone in the tryptophan-depleted state as in the control condition. Similarly, the degree of hypothermia produced by buspirone was not significantly different in the two experimental conditions. In conclusion, these results strongly suggest that the hypothermia and the increases in prolactin and growth hormone produced by buspirone are attributable to the enhanced activation of postsynaptic 5-HT1A receptors, and not to a decrease in 5-HT transmission resulting from the activation of the 5-HT1A cell body autoreceptors on 5-HT neurons.
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PMID:Serotonin 1A receptor activation and hypothermia in humans: lack of evidence for a presynaptic mediation. 1209 4

In recent years generalised anxiety disorder (GAD) has become a much better defined disorder, with specific criteria distinguishing it from the other anxiety disorders; however, it still lacks the same public and scientific interests as some of the other anxiety disorders such as panic and social phobia. Nevertheless, refinement in the treatment of GAD is becoming more evident through the conduct of clinical trials. Up until the mid-1980's, treatment consisted primarily of benzodiazepines. However, as a result of growing characterisation of their abuse potential, other therapeutic options were explored. Benzodiazepines became seen as an effective short-term therapy, and buspirone and some of the newer antidepressants have become the treatment of choice for patients with GAD requiring long-term treatment. Buspirone was the first available alternative to the benzodiazepines in the US; however, the initial excitement over this agent was somewhat dampened because of its mild efficacy combined with a slow onset of action. The antidepressants were seen as beneficial for the treatment of GAD because of the high comorbidity with depression, thus allowing a better outcome for these patients. The antidepressants that offer both a good adverse effect profile and efficacy are the selective serotonin reuptake inhibitors including paroxetine, and the serotonin-norepinephrine reuptake inhibitors such as venlafaxine. Clinicians should also consider the potential benefits of psychotherapy as an adjunct to medication. There are a number of potentially new pharmacotherapies being investigated, including newer serotonin 5-HT1A receptor agonists, cholecystokinin receptor antagonists, neurokinin receptor antagonists, gabapentin and its analogues, and gamma-aminobutyric acid (GABA)A receptor modulators. However, these compounds are all in the early stages of investigation, and there are no new therapies expected to be released in the near future. Nonetheless, in the search for the ideal anxiolytic, a more positive outlook is allowed by imminent future research for new treatment options in patients with GAD.
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PMID:Generalised anxiety disorder: treatment options. 1210 25

The effect of drug acting on 5-HT1A, 5-HT2 and 5-HT3 receptors were studied against cisplatin and apomorphine induced emesis in dogs. Buspirone, 5-HT1A receptor partial agonist significantly reduced the emetic episodes though it had no significant effect on emetic latency. Mianserin, 5-HT2 receptor antagonist exhibited significant reduction in emetic episodes and in latency. Buspirone prevented the apomorphine induced emesis while mianserin had no effect. The antiemetic activity of buspirone may be attributable to its agonistic activity at 5-HT1A receptor and antagonistic activity at dopamine receptors. These findings further confirm the involvement of 5-HT1A and 5-HT2 receptor in cytotoxic drug induced emesis, though the species difference in their antiemetic action can not be ruled out.
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PMID:Involvement of 5-HT1A and 5-HT2 receptor in cisplatin induced emesis in dogs. 1268 22


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