Ten healthy subjects received buspirone (30 mg orally) with and without pre-treatment with the 5-HT1A receptor antagonist, pindolol (80 mg over 3 days). Following pindolol treatment the growth hormone and hypothermic responses to buspirone were significantly decreased. There was also a delay in the onset of the prolactin response to buspirone but the total amount of prolactin secretion, calculated as area under the curve, was not significantly reduced. The data suggest that the growth hormone and hypothermic responses to buspirone in humans are mediated by 5-HT1A receptors, but an explanation founded on pharmacokinetic factors cannot presently be excluded. Both this latter possibility and the lack of selectivity of pindolol for 5-HT receptors indicate the need for the further neuroendocrine studies of the mode of action of buspirone, preferably with more selective 5-HT1A receptor antagonists. 相似文献
Summary Buspirone, a putative serotonin (5-HT)1A partial agonist, did not produce hypothermia in 17 normal volunteers in a placebo controlled, single blind study. Thus, buspirone may be a weaker agonist at those 5-HT1A receptors which mediate hypothermia compared to ipsapirone or gepirone, two other 5-HT1A partial agonists which have been reported to produce hypothermia by a 5-HT1A-mediated mechanism. 相似文献
Buspirone is a novel agent which is clinically effective as an anxiolytic but which lacks the muscle relaxant, anticonvulsant and sedative effects of classical anxiolytics. It also lacks the full spectrum of action of classical anxiolytics in animal models of anxiety based on shock and novelty. In the present paper the effects of buspirone and chlordiazepoxide were tested on acquisition of differential reinforcement of low rates of response (DRL). This schedule involves the suppression of behaviour by reward omission and has shown consistent effects with classical anxiolytics. Buspirone was tested at doses of 0.3, 1.1 and 3.3 mg/kg i.p. and chlordiazepoxide at 5 and 20 mg/kg. Buspirone produced effects similar to those of chlordiazepoxide on accuracy of DRL responding. However, the size of the observed effects of buspirone was small even in relation to the 5 mg/kg dose of chlordiazepoxide and did not appear to be directly related to dose. Chlordiazepoxide increased overall rate of responding, while buspirone decreased it. Buspirone appears to show only limited conformity with benzodiazepines in animal models of anxiety and this result appears independent of the reinforcer used in the task. 相似文献
The azospirones gepirone (10 mg/kg), ipsapirone (10 mg/kg) and buspirone (10 mg/kg) were examined for their effect on regional cerebral glucose utilization in conscious rats using quantitative 2-deoxyglucose autoradiography. All three 5-HT1A partial agonists reduced glucose utilization in the hippocampus and dentate gyrus by 20–25% and increased glucose utilization by 38–65% in the lateral habenular nucleus; an important relay between striatal/limbic areas and the mid-brain raphe nuclei. The findings emphasize the potential importance of the hippocampus as a site of action for 5-HT1A receptor active drugs in vivo and also suggest that functional activity in the striatal/limbichabenular-raphe pathway may be influenced by gepirone, ipsapirone and buspirone. 相似文献
The efficacy of hydroxyzine and buspirone, controlled by placebo, was investigated in a double-blind, parallel group, multicentre
study conducted in France and the UK. A total of 244 patients with generalised anxiety disorder in primary care was allocated
randomly to treatments with hydroxyzine (12.5 mg morning and mid-day, 25 mg evening), buspirone (5 mg morning and mid-day,
10 mg evening) or placebo (three capsules/day) for 4 weeks, preceded by a 1-week single-blind placebo run-in and followed
by 1-week single-blind placebo administration. Rating scales were applied on days -7,0,7,14,12,28 and 35. Seventy percent
of the patients were female; the average age was 41 ± 11 years, and the mean Hamilton Anxiety Score at day 0 was 26.5 ± 4.2.
Only 31 of the 244 patients dropped out, but equally in the three groups. Intention-to-treat LOCF analyses on the primary
variable showed a significant difference only between hydroxyzine and placebo with respect to improvement on the Hamilton
Anxiety Scale (10.75 versus 7.23 points, respectively). Secondary variables such as CGI and self-ratings (HAD scale) showed
both hydroxyzine and buspirone to be more efficacious than placebo. Thus, hydroxyzine is a useful treatment for GAD.
Received: 26 January 1998/Final version: 15 May 1998 相似文献
Fear potentiation of the acoustic startle reflex was produced by eliciting startle responses in the presence of a light that had been previously paired with a shock. Buspirone (0.6–5.0 mg/kg) and gepirone (1.25–10.0 mg/kg), but not their common metabolite, 1-PP (0.5–40 mg/kg), produced a dose-dependent reduction of fear-potentiated startle. These doses of buspirone and gepirone slightly increased baseline startle levels. Reduction of fear-potentiated startle appears to involve supraspinal sites of action, since intraventricular but not intrathecal administration of buspirone (200 ;g) reduced fear-enhanced startle. Both buspirone and gepirone were highly efficacious in this model compared to other animal tests that are used to study anxiolytic compounds. 相似文献
A high-performance liquid chromatographic (HPLC) method is described for the assay of the active metabolite [1-(2-pyrimidinyl)piperazinel of buspirone, an anxiolytic agent, in rat plasma.
The method is based on the use of ion-pair HPLC coupled to a liquid—solid extraction scheme. Samples of rat plasma (2 ml) with internal standard (1-phenylpiperazine), adjusted to pH 10.5 with borate buffer, were loaded on to a preactivated C-18 cartridge. The metabolite and the internal standard were eluted with 5 ml of methanol and injected on to a reversed-phase 10-μm Spherisorb ODS-2 column. The column was eluted with a mobile phase of 0.005 M sodium lauryl sulphate in citrate buffer (pH 3.6)-acetonitrile (65:35, v/v) at 2 ml min−1. Detection was carried out at 248 nm. The recovery of the metabolite was 55%. The method was applied to the determination of the metabolite in rat plasma after oral dosing (25 mg kg−1) of the parent compound. 相似文献
In many animal studies, acute treatment with the novel anxiolytic agent buspirone exhibits only minimal anxiolytic efficacy (i.e., increases in punished responding) when compared to benzodiazepines and barbiturates. The present studies examined the effects of acute pre-test challenges with buspirone in subjects receiving chronic post-test buspirone or saline treatments. Chronic post-test treatment with buspirone (4 mg/kg/day for 4 weeks, followed by 8 mg/kg/day for 12 weeks) did not significantly affect CSD behavior. Consistent with previous reports, acute pre-test administration of buspirone (0.125–2 mg/kg, IP) to subjects receiving chronic post-test saline treatment resulted in only a modest anti-conflict effect in the CSD paradigm (approximately ten shocks over control). In contrast, subjects chronically treated with buspirone exhibited a dramatically greater anti-conflict effect following acute challenge with buspirone (up to 40 shocks over control). These data are consistent with the hypothesis that the full anxiolytic efficacy of buspirone requires repeated administration. 相似文献
Previous work suggests that the elevated plusmaze test of anxiety is insensitive to the anxiolytic effects of the novel anxiolytic buspirone, which shows an anxiogenic-like profile in this test. This paper examines some of the possible reasons for this and the role that buspirone's agonist activity at 5-HT1A receptors plays in this effect. A variety of 5-HT1A receptor agonists (p-aminophenylethylm-trifluromethylphenyl piperazine, (+)- and (-)-MDL 72832) showed similar activity to buspirone, as did the related compound ipsapirone. (-)-MDL 72832 was more potent than (+)-MDL 72832, in keeping with its stereoselective action at 5-HT1A receptors. The 2-adrenoceptor antagonist properties of 1-pyrimidinyl piperazine, a metabolite of buspirone, did not appear to be relevant to this action of buspirone as neither it nor idazoxan showed an anxiogenic-like profile. Neither chronic treatment with buspirone (1 mg/kg SC twice a day for 16 days) nor depletion of 5-HT withp-chlorophenylalanine changed the anxiogenic-like activity of buspirone in the elevated plus-maze test. These results suggest that an agonist action at postsynaptic 5-HT1A receptors mediates the anxiogenic-like effects of buspirone in the elevated plus-maze test and that this test may either be insensitive to certain classes of anxiolytics or is measuring something unrelated to human anxiety states. 相似文献