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)

In radioligand binding studies, BIMG 80, a new putative antipsychotic, displayed good affinity at certain serotonin (5-HT1A, 5-HT2A, 5-HT6), dopamine (D1, D2L, D4), and noradrenergic (alpha1) receptors. The effect of acute subcutaneous BIMG 80, clozapine, haloperidol, risperidone, amperozide, olanzapine, and Seroquel was then investigated on dopamine release in medial prefrontal cortex, nucleus accumbens, and striatum in freely moving rats using the microdialysis technique. Four different neurochemical profiles resulted from the studies: (a) Systemic administration of BIMG 80, clozapine, and amperozide produced greater percent increases in dopamine efflux in medial prefrontal cortex than in the striatum or the nucleus accumbens. (b) Haloperidol induced a similar increase in dopamine concentrations in the striatum and nucleus accumbens with no effect in the medial prefrontal cortex. (c) Risperidone and olanzapine stimulated dopamine release to a similar extent in all brain regions investigated. (d) Seroquel failed to change significantly dopamine output both in the medial prefrontal cortex and in the striatum. Because an increase in dopamine release in the medial prefrontal cortex may be predictive of effectiveness in treating negative symptoms and in the striatum may be predictive of induction of extrapyramidal side effects, BIMG 80 appears to be a potential antipsychotic compound active on negative symptoms of schizophrenia with a low incidence of extrapyramidal side effects.
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PMID:BIMG 80, a novel potential antipsychotic drug: evidence for multireceptor actions and preferential release of dopamine in prefrontal cortex. 920 9

The antinociceptive effects of the 5-HT1A agonists buspirone [3 mg/kg intraperitoneally (i.p.)], gepirone (3-6 mg/kg i.p.), and 8-OH-DPAT [3-5 mg/kg i.p.; 1-3 micrograms per mouse intracerebroventricularly (i.c.v.)] were examined in mice by using the hot-plate (thermal stimulus) and abdominal constriction (chemical stimulus) tests. Buspirone, gepirone, and 8-OH-DPAT produced significant antinociception, which was prevented by atropine (5 mg/kg i.p.), the ACh depletor hemicholinium-3 (1 microgram per mouse i.c.v.), and the 5-HT1A antagonist NAN 190 (0.5 microgram per mouse i.c.v.), but not by naloxone (1 mg/kg i.p.), the GABAB antagonist CGP 35348 (100 mg/kg i.p.), and pertussis toxin (0.25 microgram per mouse i.c.v.). NAN 190 which totally antagonized buspirone, gepirone, and 8-OH-DPAT antinociception, did not modify the analgesic effect of morphine (5 mg/kg subcutaneously). In the antinociceptive dose range, none of the 5HT1A agonists impaired mouse performance evaluated by rota-rod and hole board tests. On the basis of these data, it can be postulated that buspirone, gepirone, and 8-OH-DPAT exert an antinociceptive effect mediated by a central amplification of cholinergic transmission.
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PMID:5-HT1A agonists induce central cholinergic antinociception. 925 13

It has been suggested that dopamine/serotonin (5-HT) imbalance, with relative enhancement of serotonergic activity, might be one of the possible pathophysiological mechanisms underlying neuroleptic-induced akathisia. On the basis of preclinical data, which imply that the partial 5-HT1A agonist buspirone possesses anti-5-HT activity, in the present open-label study we examined the putative antiakathitic effect of buspirone in 10 neuroleptic-treated patients with acute neuroleptic-induced akathisia. Buspirone (up to 30 mg/day in divided doses) was administered for a trial period of 4 days (first part of the study). No significant changes in neuroleptic-induced akathisia as rated using the Barnes Akathisia Scale were detected during buspirone treatment. Buspirone was effective in only two neuroleptic-induced akathisia patients and caused worsening of akathisia in the other two patients. According to the study design, eight buspirone non-responders were switched to the 5-HT2A/2C antagonist mianserin (15 mg/day) for the other 4 days of treatment (second part of the study). Seven mianserin-treated patients improved and five revealed complete disappearance of neuroleptic-induced akathisia. It seems that the 5-HT1A partial agonist buspirone is of limited value in the treatment of acute neuroleptic-induced akathisia. It contrast, it appears that low-dose mianserin is therapeutically effective in acute neuroleptic-induced akathisia.
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PMID:Serotonergic agents in the treatment of acute neuroleptic-induced akathisia: open-label study of buspirone and mianserin. 946 60

A method to measure various aspects of exploratory behavior was further characterized using standard pharmacological treatments known to induce anxiety, or anxiolysis, or locomotor activation. FG 7142, an anxiogenic beta-carboline, induced a dose-dependent reduction in the rat exploratory behavior. A single FG 7142 (20 mg/kg) treatment before behavioral testing had a carry-over effect on rats' behavioral performance on the two subsequent days. When FG 7142 (20 mg/kg) was administered during five consecutive days before behavioral testing, its anxiogenic-like effect first deepened, but waned off by the fifth session. Diazepam at the dose of 0.5 mg/kg had no effect of its own, but blocked the anxiogenic-like effect of FG 7142 (10 mg/kg) treatment. At a higher dose (1 mg/kg), diazepam treatment reduced exploratory behavior, but this effect was not carried over to the drug-free sessions on the subsequent day. Buspirone and gepirone (both 1 mg/kg), the 5-HT1A receptor agonists, had no effect. D-Amphetamine, a locomotion-enhancing drug which has anxiogenic-like properties in several tests of exploratory behavior, increased the activity of rats at the dose of 0.5 mg/kg, but at the dose of 1 mg/kg the only effect was a reduction in the number of rearings: this effect was not carried over to the subsequent retest. On the basis of the results described in this article and elsewhere, we suggest that this technique can be useful for separating a true anxiogenic drug from other compounds which influence exploratory activity.
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PMID:Characterization of rat exploratory behavior using the exploration box test. 958 Apr 70

Since 1990 open clinical studies and case descriptions reported full or partial antidepressant response after the addition of buspirone to various ongoing antidepressive treatments. Buspirone acts as a partial serotonin agonist at the 5-HT1A receptor. We tried to augment the effect of serotonin-selective re-uptake inhibitors (SSRI) with 30 mg buspirone in a series of 10 in-patients suffering from refractory depression. We observed two cases of partial remission and five other cases with minimal improvement but no case with complete recovery following buspirone augmentation. On the basis of our naturalistic drug surveillance in 10 refractory depressives, we cannot recommend 30 mg-buspirone augmentation of SSRI treatment in severely ill depressives.
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PMID:Weak antidepressant response after buspirone augmentation of serotonin reuptake inhibitors in refractory severe depression. 966 89

The effects of intracisternal (i.c) injections of the 5-HT1A receptor agonists, buspirone and 8-OH-DPAT, and the antagonists WAY-100635; and (-)-pindolol, the 5-HT1B/1D receptor agonist sumatriptan and antagonist GR127935, the 5-HT2 receptor agonist DOI and the antagonist cinanserin, the 5-HT3 receptor antagonist granisetron, the alpha-adrenoceptor agonist clonidine and the antagonist idazoxan, the D2 receptor antagonists (-)-sulpiride and the 5-HT uptake inhibitor fluoxetine on capsaicin-evoked increase in tracheal inflation pressure (bronchoconstriction) were investigated in alpha-chloralose anaesthetised, neuromuscularly blocked, artificially ventilated guinea-pigs. Buspirone, 8-OH-DPAT and fluoxetine significantly potentiated while WAY-100635 (-)-pindolol and sumatriptan attenuated the evoked bronchoconstriction when applied i.c. Granisetron attenuated the response when applied i.v. but not when given i.c. The 5-HT2, alpha2-adrenoceptor and D2 dopamine receptor ligands did not have any significant effect on the evoked bronchoconstriction. Pretreatment i.v. with WAY-100635 alone had no effect on the capsaicin-evoked bronchoconstriction but blocked the potentiating action of i.c. buspirone. The effects of sumatriptan could be completely blocked by pretreatment i.v. with GR127935. Only DOI, in the presence (i.v.) of the peripheral acting 5-HT2 receptor antagonist BW501C67, caused a significant increase in baseline tracheal inflation pressure. It is concluded that activation of central 5-HT1A and 5-HT1B/1D receptors have opposing roles, facilitation and inhibition respectively, on the reflex activation of bronchoconstrictor vagal preganglionic neurones.
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PMID:The role of central 5-HT receptors in the bronchoconstriction evoked by inhaled capsaicin in anaesthetised guinea-pigs. 968 Feb 49

The present series of experiments compared the behavioral effects of the novel non-peptide CRF antagonist CP-154,526 with those of diazepam and the 5-HT1A receptor partial agonist buspirone in classical animal models of anxiety including conflict tests (punished lever pressing and punished drinking tests in rats) and exploratory models (elevated plus-maze test in rats, light/dark choice and free-exploration tests in mice), and a recently developed mouse defense test battery (MDTB) which has been validated for the screening of anxiolytic drugs. Results from both conflict procedures showed that diazepam (2.5-10 mg/kg, i.p.) produced clear anxiolytic-like effects, whereas buspirone (2.5 mg/kg, i.p.) displayed anticonflict activity in the punished drinking test only. CP-154,526 (0.6-20 mg/kg) was devoid of significant activity in both procedures. In the elevated plus-maze, diazepam (2 mg/kg, i.p.) produced significant effects on traditional (i.e. spatio-temporal) and ethologically derived (i.e. risk assessment and directed exploration) indices of anxiety. Buspirone (1-4 mg/kg, i.p.) reduced risk assessment activities only, and CP-154,526 (0.6-20 mg/kg, i.p.) did not modify the indices of anxiety in the elevated plus-maze. In the light/dark test, diazepam (2.5-5 mg/kg, i.p.) and CP-154,526 (10-40 mg/kg, i.p.) affected all behavioral indices of anxiety, while buspirone reduced risk assessment activities at the highest doses only (10 and 15 mg/kg, i.p.). In the free-exploration test, diazepam (1 mg/kg, i.p.) reduced avoidance responses towards novelty, as indicated by the increase in exploratory activity in a novel compartment and the decrease in risk assessment. CP-154,526 failed to affect the former behavior and weakly reduced the latter (5 and 20 mg/kg, i.p.). Buspirone (1.25-5 mg/kg, i.p.) was inactive in this test. Finally, in the MDTB, diazepam (0.5-3 mg/kg, i.p.) attenuated all defensive reactions of mice confronted with a rat stimulus (i.e. flight, risk assessment and defensive attack) or with a situation associated with this threat (i.e. contextual defense). Buspirone (1.25-5 mg/kg, i.p.) reduced defensive attack and contextual defense, while CP-154,526 (5-20 mg/kg, i.p.) affected all defensive behaviors, with the exception of one risk assessment measure. The finding that CP-154,526 displayed positive effects in mice but not in rats may be due to increased sensitivity to environmental stress of the strains used (i.e. BALB/c, Swiss) and/or to the fact that animals were exposed to unavoidable stress stimuli which may lead to a significant activation of the CRF system. Although in mice the anxiety-reducing potential of CP-154,526 is superior to that of the atypical anxiolytic buspirone, it is smaller in terms of the magnitude of the effects and the number of indices of anxiety affected than that of diazepam.
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PMID:Characterization of the behavioral profile of the non-peptide CRF receptor antagonist CP-154,526 in anxiety models in rodents. Comparison with diazepam and buspirone. 969 27

Our previous study showed that the serotonergic system was involved in the ethanol-induced striatal ascorbic acid release in rat. In the present study, the 5-HT1A agonists and antagonists were used to analyze the possible mechanism of ethanol-induced ascorbic acid release in rat striatum. The results showed that ethanol (3.0 g/kg, i.p.) significantly increased striatal ascorbic acid release. Buspirone (5.0 mg/kg, s.c.), a partial agonist of 5-HT1A receptors, and 8-OH-DPAT (0.5 mg/kg, s.c.), a selective agonist of 5-HT1A receptors, showed no effect on basal ascorbic acid release in striatum, but both drugs significantly antagonized the ascorbic acid release induced by ethanol in striatum. WAY 100635 (0.5 mg/kg, s.c.), a selective antagonist of 5-HT1A receptors, affecting neither the basal nor the ethanol-induced ascorbic acid release per se, antagonized the suppressing effect of 8-OH-DPAT on ethanol-induced ascorbic acid release in striatum. This study gives the first evidence that activation of 5-HT1A receptors is involved in ethanol-induced ascorbic acid release in rat striatum.
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PMID:5-HT1A receptors mediate inhibition of ethanol-induced ascorbic acid release in rat striatum studied by microdialysis. 969 27

Alnespirone (S 20499) has previously been described as a potential anxiolytic drug that acts by stimulation of 5-HT1A receptors. Some data suggest that alnespirone might also be a weak dopamine D2 receptor agonist: it displays moderate affinity for dopamine D2 receptors in vitro and it inhibits prolactin release and induces yawning in rats. In order to test for possible interactions of alnespirone with dopamine receptors in vivo, we studied the changes of in vivo striatal [3H]SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zepine) and [3H]raclopride binding following the injection of a tracer dose of either tritiated ligand (4 microCi) in mice treated with increasing doses of alnespirone (5, 10, 20 and 40 mg/kg, i.p.) and, in the same animals, the changes in the levels of dopamine, 5-hydroxytryptamine (5-HT) and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA). These changes were compared with those produced by increasing doses of the reference 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin, 0.25, 1 and 4 mg/kg, i.p.) or buspirone (5 and 20 mg/kg, i.p.). Decreased in vivo striatal [3H]SCH 23390 specific binding was observed in mice treated with 5, 10 and 40 mg/kg alnespirone. In contrast, increased in vivo striatal [3H]raclopride specific binding was observed in mice treated with 5 and 20 mg/kg alnespirone. In these animals, the striatal 5-HIAA/5-HT ratio was decreased by 5 to 40 mg/kg alnespirone, whereas the striatal HVA/DA ratio was unaffected at all tested doses of alnespirone. Similarly, 8-OH-DPAT decreased specific in vivo striatal [3H]SCH 23390 binding at 0.25, 1 and 4 mg/kg, and increased in vivo specific striatal [3H]raclopride binding at 1 and 4 mg/kg. In the same animals, all tested doses of 8-OH-DPAT decreased the striatal 5-HIAA/5-HT ratio but did not modify the striatal HVA/dopamine ratio. Buspirone (5 and 20 mg/kg) completely inhibited in vivo specific striatal [3H]raclopride binding and increased the striatal HVA/DA ratio but did not modify the striatal 5-HIAA/5-HT ratio, whereas apomorphine (3 mg/kg) decreased both in vivo specific striatal [3H]SCH 23390 and [3H]raclopride binding as well as the striatal HVA/DA and 5-HIAA/5-HT ratios. Finally, increasing doses of alnespirone or 8-OH-DPAT weakly increased sniffing induced by apomorphine (0.75 mg/kg, s.c.) in mice and decreased grooming induced by the dopamine D1 receptor agonist SK&F 39393 ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol, 1.87 mg/kg, s.c.), whereas buspirone decreased both apomorphine-induced sniffing and SK&F 39393-induced grooming. These results indicate that alnespirone and 8-OH-DPAT have a similar profile and do not seem to interact directly with dopamine receptors. The results also suggest that the stimulation of 5-HT1A receptors by either alnespirone or 8-OH-DPAT modulates the availability of striatal [3H]SCH 23390 and [3H]raclopride binding sites and possibly the functioning of striatal dopamine D1 and D2 receptors in opposite directions.
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PMID:Similar pharmacological properties of 8-OH-DPAT and alnespirone (S 20499) at dopamine receptors: comparison with buspirone. 971 53

1. The effects of central application of 5-HT1A and 5-HT1B/1D receptor ligands on the reflex bradycardia, apnoea, renal sympathoexcitation and pressor response evoked by stimulating upper airway receptors with smoke in atenolol-pretreated anaesthetized rabbits were studied. 2. Intracisternal administration of the 5-HT1A receptor antagonists WAY-100635 (100 microg kg(-1)) and (-)pindolol (100 microg kg(-1)) significantly reduced the smoke-induced bradycardia, attenuated the pressor response and in the case of (-)pindolol, sympathetic nerve activity. The same dose of WAY-100635 i.v. was without effect. 3. Buspirone (200 microg kg(-1), i.c.) potentiated the reflex bradycardia. This action was prevented if the animals were pretreated with WAY-100635 (100 Hg kg(-1), i.v.) 4. (+)8-OH-DPAT (25 microg kg(-1), i.c.) attenuated the evoked bradycardia, pressor response, apnoea and renal sympathoexcitation. The attenuation of the apnoea and renal sympathoexcitation, but not the bradycardia or pressor response was prevented in animals pretreated with WAY-100635 (100 microg kg(-1), i.v.). The attenuation of the reflex bradycardia and the reduction in the renal sympathoexcitation were reduced by pretreatment with the 5-HT1B/1D receptor antagonist GR127935 (100 microg kg(-1), i.v.). 5. In WAY-100635 (100 microg kg(-1), i.v.) pretreated animals, sumatriptan (a 5-HT1B/1D receptor agonist) reduced the reflex bradycardia and the pressor response. The 5-HT1B/1D receptor antagonist GR127935 (20 microg kg(-1), i.c. or 100 microg kg(-1), i.v.) had no effect on the reflex responses. 6. In conclusion, the present data are consistent with the hypothesis that activation of central 5-HT1A receptors potentiate whilst activation of 5-HT1B/1D receptors attenuate the reflex activation of cardiac preganglionic vagal motoneurones evoked by stimulation of upper airway receptors with smoke in rabbits.
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PMID:Modulation of the vagal bradycardia evoked by stimulation of upper airway receptors by central 5-HT1 receptors in anaesthetized rabbits. 978 16


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