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 pharmacological characteristics of hindlimb scratching induced by serotonergic compounds were studied. We conclude that hindlimb scratching induced by serotonergic compounds is mediated by a serotonin1D (5-HT1D) or 5-HT1D-like receptor outside the blood-brain barrier because hindlimb scratching could be induced by s.c. injection of 5-methoxytryptamine (5-MeOT), 5-carboxamidotryptamine (5-CT), bufotenine, 5-hydroxytryptamine (5-HT) and tryptamine. These compounds have high affinity for 5-HT1A and 5-HT1D receptors. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT1C receptor agonist MK 212, and the mixed 5-HT1C/5-HT2 receptor agonists (dl)-1-(2,5 dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and quipazine did not induce hindlimb scratching. Rather, the latter compounds attenuated 5-MeOT-induced hindlimb scratching. The 5-HT releasing compounds fenfluramine and p-chloroamphetamine (PCA) inhibited whereas the 5-HT re-uptake inhibitors fluvoxamine and indalpine potentiated 5-MeOT-induced hindlimb scratching. 5-MeOT-induced hindlimb scratching could be inhibited dose dependently by the alpha 2-adrenoceptor blockers yohimbine and rauwolsince, which also have high affinity for 5-HT1D receptors, whereas the alpha 2-adrenoceptor blocker piperoxan only weakly counteracted hindlimb scratching. Haloperidol, apomorphine, morphine, clonidine and methiothepin strongly attenuated hindlimb scratching, atropine, naloxone and ICS 205930 attenuated it weakly whereas domperidone, methylatropine and mepyramine were inactive in doses up to 10 mg/kg. Hindlimb scratching induced by 5-MeOT was potentiated by the 5-HT receptor antagonists metergoline, methysergide, mesulergine, mianserin, ritanserin and xylamidine. Hindlimb scratching was not induced by i.c.v. injection of 5-MeOT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A peripheral 5-HT1D-like receptor involved in serotonergic induced hindlimb scratching in rats. 206 Jun 1

The involvement of the 5-HT1A receptor in the 5-HT syndrome (head weaving and hindlimb abduction) induced in DBA mice by tryptamine was investigated. Methysergide, (-)propranolol and spiperone suppressed both the head weaving and hindlimb abduction induced by tryptamine. However, ketanserin and ICS 205-930 did not affect them. Haloperidol induced small decreases in the head weaving, but had no effect on the hindlimb abduction. These results indicate that the 5-HT syndrome induced by tryptamine in mice is mediated by the 5-HT1A receptor. Therefore, 5-HT syndrome may also be associated with the 5-HT1A receptor in mice, as it is in rats.
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PMID:The evidence for the involvement of the 5-HT1A receptor in 5-HT syndrome induced in mice by tryptamine. 262 95

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)
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PMID:Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured ex vivo by quantitative autoradiography. 751 May 74

The effects of chronic treatment of rats with RWJ 37796, a novel aryl-piperazine containing antipsychotic drug, on brain monoamine receptors were studied. Rats were treated daily with RWJ 37796 (1.3 mg/kg), the typical antipsychotic haloperidol (1 mg/kg) or vehicle (control) for 21 days, and were sacrificed 3 days after the last injection. Binding of [3H]Sch-23390 and [3H]spiperone to D1 and D2 dopamine receptors, respectively, and [3H]8-hydroxy-2-(di-n-propylamino)-tetralin ([3H]8OH-DPAT) to 5-HT1A receptors were measured in various brain regions using quantitative autoradiography. Binding to D2 dopamine receptors was significantly elevated in the caudate-putamen of rats treated with haloperidol or RWJ 37796 as compared to controls. However, the magnitude of the increase in D2 binding was significantly greater in haloperidol-treated (+38%) compared to RWJ 37796-treated (+21%) rats. Haloperidol treatment also increased binding (+35%) to D2 dopamine receptors in the nucleus accumbens, where RWJ 37796 treatment had a considerably smaller effect (+12). No changes in D1 dopamine or 5-HT1A receptor binding were detected following either antipsychotic treatment in any brain regions studied. Thus, at comparable doses, the novel antipsychotic RWJ 37796 produces less up-regulation of D2 dopamine receptor binding in the striatum than does the typical antipsychotic haloperidol.
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PMID:The effect of chronic treatment with a novel aryl-piperazine antipsychotic on monoamine receptors in rat brain. 755 50

There are numerous preclinical screening procedures that are predictive of clinical efficacy for the positive symptoms of schizophrenia but no assays for the negative symptoms such as social withdrawal. In the social interaction test in rats, the atypical antipsychotic drug clozapine (10.0 mg/kg) and two putative atypical agents risperidone (0.0625 mg/kg) and HP 873 (0.5 and 1.0 mg/kg) significantly increased social interaction behaviors between pairs of unfamiliar but not familiar rats. The benzodiazepine diazepam (1.25-5.0 mg/kg) increased social behaviors in both paradigms. Haloperidol, chlorpromazine, raclopride, and SCH23390 decreased social behaviors in these assays. In vitro receptor binding studies revealed that only clozapine, risperidone, and HP 873 displayed dopamine to serotonin affinity ratios for both D2/5-hydroxytryptamine2(5-HT2)/ and D1/5-HT1A of greater than or equal to 12.9 and 1.0, respectively. The present study suggests that antipsychotic agents that may be effective in social withdrawal can be identified in this modified social interaction paradigm. Further, our data suggests that a compound's effectiveness for the treatment of social withdrawal is at least in part due to its relative affinity for binding to dopamine D1 and serotonin 5-HT1A receptors.
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PMID:Effects of atypical antipsychotic agents on social behavior in rodents. 768 16

To investigate a dopaminergic component in the discriminative stimulus properties of buspirone, rats were trained to discriminate 2.5 mg/kg buspirone from saline, using a two lever, food-rewarded, fixed ratio 10 operant procedure. To test the dopamine-2 (D2) antagonist action of buspirone, a second group of rats was trained to discriminate 0.16 mg/kg apomorphine from saline. In addition to a complete generalization to 8-OH-DPAT, the D2 antagonists haloperidol, R 79598 and sulpiride showed a partial generalization to buspirone. The benzodiazepine ligands chlordiazepoxide and bretazenil did not generalize to the buspirone cue. Buspirone (2.0 mg/kg) completely blocked the apomorphine cue in the apomorphine trained rats. Haloperidol, R 79895 and sulpiride also blocked the apomorphine cue, although at doses much smaller than the doses needed to evoke buspirone responding in the buspirone trained group. 8-OH-DPAT did not antagonize apomorphine. It was concluded that the D2 action of buspirone partially contributes to its discriminative stimulus properties. Mediation of the buspirone cue by 5-HT1a receptor activation seemed predominant. Further, buspirone can act as a full D2 antagonist in drug discrimination. A model was proposed suggesting a compound discriminative stimulus complex of buspirone with a dominant 5-HT1a component that overshadows a less pronounced D2 component.
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PMID:The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity. 787 Sep 34

The partial DA receptor agonist preclamol, (-)-3-PPP (50-200 mumol/kg, s.c.) partially reversed the catalepsy induced by the dopamine (DA) receptor antagonists haloperidol (5.3 mumol/kg, i.p.) and raclopride (20.1 mumol/kg, i.p.) in rats. Terguride (transdihydrolisuride), a partial DA receptor agonist with an efficacy lower than that of preclamol, blocked haloperidol (10.6 mumol/kg, i.p.) induced catalepsy at 5 mumol/kg, s.c., but not at 20 mumol/kg, s.c. The effects of terguride in this assay are possibly related to the compound's mixed partial DA agonist/5-HT1A receptor agonist properties. The high efficacy agonist, pramipexole (SND 919) also blocked haloperidol induced catalepsy at 50 mumol/kg, s.c. Haloperidol (0.33-1.3 mumol/kg, i.p.) reduced the locomotor activity down to 5% of saline controls and elevated limbic and striatal DOPA accumulation. When combined with haloperidol, preclamol (100-200 mumol/kg, s.c.) antagonized both the strong hypomotility and increase in DOPA accumulation. Finally, the elevation of serum prolactin in rats induced by haloperidol (0.25 mumol/kg, i.p.) was significantly antagonized by co-administration of preclamol (39 mumol/kg, s.c.). These results show that partial DA agonists can reverse both behavioral, biochemical and neuroendocrine effects of neuroleptics. It also suggests the utility of partial DA receptor agonists in combination with classical neuroleptics in order to minimize the appearance of extrapyramidal side-effects and hyperprolactinemia.
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PMID:Partial dopamine receptor agonists reverse behavioral, biochemical and neuroendocrine effects of neuroleptics in the rat: potential treatment of extrapyramidal side effects. 790 92

The 5-HT1A receptor agonists buspirone, 8-hydroxy-N,N-dipropyl-2-aminotetralin, gepirone and ipsapirone were evaluated for their receptor binding profiles and their effects on firing rates of 5-HT, dopamine (DA) and noradrenaline (NA) neurons in the dorsal raphe, substantia nigra pars compacta and the locus ceruleus, respectively. All agents bound to 5-HT1A receptors with high affinities. All agents also bound to dopamine D2 receptors but, with the exception of buspirone, affinities were usually much lower than for 5-HT1A receptors. All agents depressed 5-HT neurons, with 8-hydroxy-N,N-dipropyl-2-aminotetralin having a potency about 8 to 12 times those for the other three. All agents also antagonized the inhibition of DA neurons by amphetamine, an index of DA antagonist properties. Buspirone reversed amphetamine's effects with doses similar to those for depressing 5-HT neurons, but the remaining three required much higher doses to affect DA neuron function. All four 5-HT1A agonists excited NA neurons. In each case, doses required for excitation of NA cells were similar to those reversing amphetamine's effects on DA cells, but not to those for depressing 5-HT cells. Haloperidol also stimulated NA cells. It is concluded that excitation of NA neurons by 5-HT1A agonists may be due to interactions with dopaminergic, rather than serotonergic, receptors.
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PMID:Excitation of noradrenergic cell firing by 5-hydroxytryptamine1A agonists correlates with dopamine antagonist properties. 813 43

The i.v. administration of the 5-hydroxytryptamine (5-HT)1A antagonist spiperone (1 mg/kg) antagonized the suppressant effect of microiontophoretic applications of 5-HT and of the selective 5-HT1A agonist 8-OH-DPAT on the firing activity of the rat dorsal raphe 5-HT neurons. In contrast, the same dose of spiperone did not alter the responsiveness to microiontophoretic applications of 5-HT and 8-OH-DPAT of pyramidal neurons in the CA3 region of the hippocampus, therefore indicating that spiperone does not act as a classical antagonist at these postsynaptic 5-HT1A receptors. After two daily injections of spiperone (5 mg/kg, i.p.) and a third one immediately before the experiment, the responsiveness of CA3 pyramidal neurons to 5-HT applied by microiontophoresis and to that released by the electrical stimulation of the ascending 5-HT pathway was markedly reduced. After 24, but not 12 or 48 h after a single injection of spiperone (5 mg/kg, i.p.), the responsiveness to exogenous and endogenous 5-HT was decreased. Smaller doses (1 and 2.5 mg/kg, i.p.) were ineffective. Haloperidol and ketanserin (5 mg/kg, i.p., 24 h before the experiment) were ineffective in blocking the responsiveness of CA3 pyramidal neurons to 5-HT, thereby demonstrating that the dopamine D2 and 5-HT2 properties of spiperone could not account for the attenuated responsiveness of the hippocampus neurons to 5-HT. Methiothepin (5 mg/kg, i.p., 24 h before recording), as for spiperone, antagonized the suppressant effect of 5-HT applied by microiontophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: I. Effect of spiperone. 847 32

SM-9018 (cis-2-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl) hexahydro-1 H-isoindole-1,3(2H)-dione HCl) is a potential atypical antipsychotic with high affinity for 5-HT2, dopamine D2 and 5-HT1A receptors. Northern blot analysis was performed to compare the effects of SM-9018 and of haloperidol on the striatal c-fos mRNA expression in rats. Haloperidol (0.3-30 mg/kg, p.o.) markedly increased the striatal c-fos mRNA levels (about eight-fold at 30 mg/kg), the increase being abolished by lesioning of dopamine neurons with 6-hydroxydopamine. In contrast, SM-9018 produced only a slight increase (about two-fold) in c-fos mRNA expression at doses up to 30 mg/kg (p.o.). The 5-HT2 receptor antagonist, ritanserin (0.1-3 mg/kg, i.p.), dose-dependently attenuated the haloperiodol-induced c-fos expression, but the putative 5-HT1A receptor antagonist, NAN-190 (1-(2-methoxyphenyl)-4-(4-(2-phethalimmido)butyl)piperazine HBr; 1-10 mg/kg, i.p.), did not. These findings suggest that SM-9018 is weaker than haloperidol for induction of striatal c-fos mRNA expression, to which the 5-HT2 receptor blocking activity of SM-9018 seems to contribute.
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PMID:Contrasting effects of SM-9018, a potential atypical antipsychotic, and haloperidol on c-fos mRNA expression in the rat striatum. 881 76


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