Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:Buspirone: an update on a unique anxiolytic agent. 304 84

Buspirone (Buspar; Bristol) marks a departure from established concepts of anxiolysis. Differing substantially both in its mode of action and in the clinical expression of its action from agents such as barbiturates and benzodiazepines, it would seem to operate chiefly via the 5-HT1A subtype of serotonin receptor. Such receptor selectivity is likely to be responsible for the novel action of this anxiolytic in that sedation and psychomotor and cognitive dysfunction are minimal, and because dependence is unlikely. The slower onset of full therapeutic benefit further delineates the differences between buspirone and other anxiolytics. However, it is apparent that the benzodiazepines will not readily be displaced from all of their varied applications by buspirone. This review examines buspirone and provides some guidelines for its use.
 ...
PMID:Buspirone--frontrunner of a new genre of anxiolytics. 305 61

Groups of rats were treated with buspirone (1 mg/kg/day) for 21 days using osmotic minipumps implanted subcutaneously. After buspirone treatment, the 5-HT1A receptor mRNA levels were significantly decreased in the CA1 and CA2 of the hippocampus, but were markedly increased in the dentate gyrus (DG), CA3 and CA4. The level of the 5-HT1A receptor binding sites was not significantly changed in these subhippocampal areas. Buspirone treatment markedly increased 5-HT2A receptor mRNA levels in the DG, CA2, CA3 and CA4. This was accompanied by a significant increase in the level of 5-HT2A receptor binding sites in all subhippocampal regions. These results demonstrate that chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA as well as their expressed binding sites in various regions of the hippocampus.
 ...
PMID:Chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA and binding sites in various regions of the rat hippocampus. 750 Aug 48

Risperidone (Risperdal) is a novel antipsychotic drug, with beneficial effects on both positive and negative symptoms of schizophrenia, and with a low incidence of extrapyramidal side effects (EPS). These particular properties have been attributed to the predominant and very potent serotonin 5-HT2 receptor antagonism of the drug combined with less potent dopamine D2 antagonism. In order to provide data on the degree to which various central neurotransmitter receptors are occupied in vivo, we performed ex vivo receptor occupancy studies with risperidone in comparison with clozapine and haloperidol in rats and guinea pigs. Various types of receptors, to which the compounds were known to bind to in vitro, were investigated precisely using receptor autoradiography in sections of the same rat brain except for histamine H1 receptors that were measured in the guinea-pig cerebellum. Risperidone (2 h after s.c. treatment) occupied 5-HT2 receptors at very low doses (ED50 = 0.067 mg/kg). Nearly full occupancy (> 80%) was achieved before H1, D2, alpha 1 and alpha 2 receptors became occupied (ED50 = 0.45, 0.66, 0.75 and 3.7 mg/kg, respectively). Clozapine displayed occupancy of H1 and alpha 1 receptors at low doses (ED50 = 0.15 and 0.58 mg/kg, respectively) and of 5-HT2, 5-HT1C, D2, alpha 2, cholinergic muscarinic and 5-HT1A receptors at higher doses (ED50 = 1.3, 1.8, 9.0, 9.5, 11 and 15 mg/kg, respectively). Haloperidol occupied D2 and alpha 1 receptors at low doses (ED50 = 0.13 and 0.42 mg/kg, respectively) and 5-HT2 receptors at a higher dose (ED50 = 2.6 mg/kg). Occupancy of receptor types occurred with similar ED50-values in various brain areas, e.g. D2 receptors in striatum and mesolimbic areas. The ED50-values for the ex vivo measured occupancy of 5-HT2 and D2 receptors were in good agreement with ED50-values for functional effects putatively mediated by these central receptors. The dose-dependent occupancy of D2 receptors proceeded more gradually with risperidone (slope in the caudate-putamen: 0.85) than with clozapine (slope: 1.44) or haloperidol (slope: 1.51). It has previously been suggested that partial D2 receptor occupancy may suffice to control the positive symptoms of schizophrenia, whereas higher D2 receptor occupancy would induce extrapyramidal symptoms (EPS). The dose ratio for high (75%) vs. low (25%) D2 receptor occupancy in the caudate-putamen, was 37.3 for risperidone, 8.4 for clozapine, and 7.9 for haloperidol.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured ex vivo by quantitative autoradiography. 751 May 74

Buspirone, an agonist of the 5-HT1A subtype of serotonin receptors, has shown antiemetic activity in animal models. However, in cancer patients treated with cisplatin, ondansetron, given either i.v. (one 8-mg dose 30 min after cisplatin) or orally (one 16-mg dose at the end of cisplatin infusion) was superior (P < 0.001) to buspirone (60 mg p.o. at the end of cisplatin and 60 mg p.o., 30 min later), in all parameters of antiemetic efficacy. These results are in favour of 5-HT3 receptors, but against the participation of 5-HT1A receptors in acute emesis associated with cisplatin chemotherapy.
 ...
PMID:Comparative efficacy of a single oral dose of ondansetron and of buspirone against cisplatin-induced emesis in cancer patients. 754 13

The radioligand [3H]YM-09151-2 ((+/-)-cis-N-(1-benzyl-2- methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylamino benzamide) was used to study the binding of various antipsychotic agents. Saturation experiments showed that [3H]YM-09151-2 labelled a single population of binding sites in both the olfactory tubercle and the striatum (dissociation constants (KD): 36 +/- 3 pM and 26 +/- 2 pM, respectively). The total number of binding sites (Bmax) was greater in the striatum than in the olfactory tubercle (18.1 +/- 1.8 fmol/mg tissue and 5.3 +/- 0.9 fmol/mg tissue respectively). Risperidone and thioridazine displaced [3H]YM-09151-2 in a biphasic manner in both brain regions, and clozapine also produced biphasic displacement curves in the olfactory tubercle but not in the striatum. All other dopamine D2 receptor antagonists tested displaced [3H]YM-09151-2 in a monophasic manner in both brain regions, in agreement with previously published data. Biphasic displacement did not appear to result from interactions with either the dopamine D3, dopamine D4, 5-HT2, 5-HT1C or the 5-HT1A receptor binding sites. It is suggested that thioridazine, risperidone and clozapine might discriminate between different affinity states and/or subtypes of the dopamine D2 receptor which may be different from the recently identified D2short and D2long receptors.
 ...
PMID:Biphasic displacement of [3H]YM-09151-2 binding in the rat brain by thioridazine, risperidone and clozapine, but not by other antipsychotics. 768 73

1. We devised a new light/dark transition apparatus, recorded transitions, % time animals spent outside the dark chambers (% time) and locomotor activity, and evaluated this apparatus by testing anxiolytics, non-anxiolytic drugs and putative anxiogenic drugs in mice. 2. Diazepam and alprazolam significantly increased transitions, % time and locomotor activity. The effects of 1 mg/kg (i.p.) diazepam on these parameters in this modified test were blocked by flumazenil, a selective benzodiazepine antagonist. 3. Anxiogenic drugs such as beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) and picrotoxin significantly decreased all three parameters. Another anxiogenic drug, yohimbine, also significantly decreased transitions and locomotor activity, but it significantly increased % time at 5 mg/kg (i.p.). 4. Imipramine (5-10 mg/kg, i.p.), an antidepressant, sulpiride (10-25 mg/kg, i.p.), an antipsychotic drug, and scopolamine (0.1-1 mg/kg, i.p.), an anticholinergic drug, had no effect. 5. Buspirone, a partial 5-HT1A receptor agonist, produced parameter changes similar to those induced by anxiolytic benzodiazepines. 8-OH-DPAT, a full 5-HT1A receptor agonist, significantly increased transitions and locomotor activity but not % time. 5-HT3 receptor antagonists, ICS205-930 and MDL72222, did not have any effect on these parameters. 6. Methamphetamine (1-2 mg/kg, i.p.) increased all parameters, while caffeine increased only locomotor activity. 7. The present findings indicate that the modified light/dark transition test is very simple and easy to perform for testing the anxiolytic and anxiogenic effects of drugs.
 ...
PMID:The modified light/dark transition test in mice: evaluation of classic and putative anxiolytic and anxiogenic drugs. 771 61

Hippocampal rhythmical slow activity (RSA) can be elicited by stimulation of the midbrain reticular formation. Buspirone, chlordiazepoxide and imipramine are all anxiolytic and have all been shown to decrease the frequency of RSA. All these compounds have been suggested to affect, directly or indirectly, 5-HT metabolism and function. The present experiments tested the possibility that buspirone, chlordiazepoxide and imipramine reduce RSA frequency via 5-HT1A autoreceptors. Rats received buspirone (10 mg/kg), chlordiazepoxide (5 mg/kg) and imipramine (30 mg/kg) after 5-HT depletion with p-chlorophenylalanine (pCPA, 100 mg/kg/day for 3 days or 350 mg/kg/day for 2 days) or after pretreatment with 5-HTP (40 mg/kg, to replete 5-HT) as well as pCPA. The frequency-reducing effects produced by buspirone and chlordiazepoxide were unchanged by either dose of pCPA, whereas the frequency-reducing effect of imipramine was completely eliminated by the high dose of pCPA. Pindolol, but not beta-blockers (a combination of metoprolol and ICI118,551), was able to block the effect of imipramine on RSA frequency. Pindolol has been reported to block the effects of buspirone but not chlordiazepoxide. These data suggest that: (1) buspirone obtains its frequency-reducing effects via pre- or post-synaptic 5-HT1A receptors rather than 5-HT1A autoreceptors; (2) chlordiazepoxide obtains its frequency-reducing effect via benzodiazepine receptors and GABA with no direct or indirect involvement of 5-HT systems; and (3) imipramine obtains its frequency-reducing effect by increasing the availability of 5-HT at 5-HT1A receptors which are not autoreceptors.
 ...
PMID:The interaction of serotonin depletion with anxiolytics and antidepressants on reticular-elicited hippocampal RSA. 776 Sep 82

Buspirone is renowned for its highly inconsistent effects in animal models of anxiety. In the present study, the effects of acute (0.63-5.0 mg/kg) and chronic (1.25-5.0 mg/kg, daily, 15 days) buspirone treatment on the behaviour of mice in the elevated plus-maze test were assessed using a recently developed ethological scoring method. On acute administration, a selective reduction in risk assessment behaviours was observed at 1.25 mg/kg; these mild anxiolytic-like effects were maintained at higher doses (2.5-5.0 mg/kg) which also reduced measures of general activity. Similar, though more potent, effects were observed with chronic administration; the lowest dose tested (1.25 mg/kg) reduced open arm entries and total stretch attend postures while higher doses profoundly reduced all major indices of anxiety (traditional and novel) and, concomitantly, suppressed total entries and rearing. Acute administration of haloperidol (0.0125-0.1 mg/kg) appeared to mimic the behavioural suppressant effects of buspirone without selectively affecting anxiety-related measures at any dose. It is suggested that the anti-anxiety and behavioural suppressant profile of buspirone may reflect combined action at 5-HT1A and D2 receptors, respectively. Results are discussed in relation to the utility of risk assessment as a sensitive index of anxiety in models based upon unconditioned behaviour.
 ...
PMID:Ethological evaluation of the effects of acute and chronic buspirone treatment in the murine elevated plus-maze test: comparison with haloperidol. 783 22

The effects of the putative anxiolytic agent buspirone on food-handling behavior of laboratory rats were investigated. Rats trained to travel from a covered shelter to a food source were provided with food pellets of six sizes. Smaller pellets were eaten at the exposed food source, whereas larger pellets were carried back to the shelter for consumption. Subcutaneous administration of buspirone hydrochloride (0.2-2.0 mg/kg) reduced carrying of larger food pellets in a dose-dependent manner. Instead, these pellets were also eaten at the exposed food source. Carrying was maximally suppressed 1 h after drug administration. Handling of smaller pellets, travel times, and eating times were not affected by buspirone. Similar results have previously been obtained with diazepam. Buspirone appears to exert its effects through 5-HT1A and/or dopamine receptors, whereas diazepam interacts with benzodiazepine receptors. Thus, manipulations of distinct transmitter systems may have similar behavioral consequences on the food carrying responses of rats.
 ...
PMID:Food carrying in rats is blocked by the putative anxiolytic agent buspirone. 786 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>