Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:110-85-0 (piperazine)
 5,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 5-hydroxytryptamine (5-HT) receptor mediating endothelium-dependent relaxation of pig coronary arteries was characterized using a variety of 5-HT receptor agonists and antagonists. Unrubbed (with endothelium preserved) rings precontracted by prostaglandin F2 alpha in the presence of ketanserin relaxed in an endothelium-dependent manner to 5-HT, 5-carboxamidotryptamine and 5-methoxytryptamine with about equal potency and efficacy. By comparison, bufotenine, 3-(dimethylamino)ethyl-N-methyl-1H-indole-5-methane sulfonamide, (-)-alpha-methyl-5-HT,N,N-dipropyl-5-carboxamidotryptamine and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole were half-efficient and other drugs [in particular the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin] were inactive as agonists up to 0.1 mM. The effect of 5-carboxamidotryptamine was antagonized in an apparently competitive manner by 15 drugs. Among the most potent antagonists (mean pKB value) were the nonselective 5-HT receptor antagonists, methiothepin (7.30) and metergoline (6.86), the 5-HT1A/5-HT1D receptor ligand, 1-[2-(4-amino-phenyl)ethyl]-4-(3-trifluoromethylphenyl)-piperazine (7.02), the 5-HT1A/5-HT1B/5-HT1D receptor ligand, 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2,-a]quinoxaline 1 (6.73) and yohimbine (6.37). Selective ligands for 5-HT1A receptors were either inactive [8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide] or poorly active (spiperone, 4.44). Beta-adrenoceptor antagonists with affinity for 5-HT1A and 5-HT1B receptors weakly antagonized the effect of 5-carboxamidotryptamine (pKB values less than or equal to 5.32), as did the 5-HT1c/5-HT2 receptor antagonist, mesulergine (5.30) and the yohimbine isomer, corynanthine (4.85). Methysergide was clearly a noncompetitive antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5-Hydroxytryptamine (5-HT)-induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT1D receptor subtype. 213 76

1. Different 5-hydroxytryptamine (5-HT) receptor subtypes mediate different behavioural responses. Compounds acting at more than one 5-HT receptor exert behavioural effects which may be the result of response competition or a specific interaction between pathways within the CNS. Therefore the mutual interaction between different 5-HT receptor subtypes was studied. 2. Hypothermia and hypoactivity in mice induced by the 5-HT1A-agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) could be attenuated by the preferential 5-HT1C-agonists MK 212, 1-(meta-chlorophenyl)-piperazine (mCPP) and m-trifluoromethyl phenyl piperazine (TFMPP), and by the mixed 5-HT2/1C-agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The mixed 5-HT1A/1B-agonist CGS 12066B at 10 mg kg-1 potentiated hypothermia and had no effect on hypoactivity. 3. Forepaw treading in rats induced by the 5-HT1A-agonist 8-OH-DPAT was attenuated by the 5-HT1C-agonists MK 212 and mCPP. The 5-HT1C-agonist TFMPP had a bimodal effect: at low doses (less than 1 mg kg-1) it potentiated, and at higher doses (greater than 2.2 mg kg-1) it attenuated forepaw treading, the mixed 5-HT2/1C-agonist DOI produced 5-HT2-related behaviours and potentiated 8-OH-DPAT-induced forepaw treading. This indicates an attenuating effect of 5-HT1C-receptor activation and a potentiating effect of 5-HT2-receptor activation. CGS 12066B had no effect in this respect. 4. Head shakes in rats induced by DOI could be attenuated by 8-OH-DPAT, TFMPP, mCPP and MK 212. The ID50S were 0.03, 0.7, 0.1 and .2 mg kg-1, respectively. This suggests that a 5-HT2-receptor-mediated effect may be attenuated by activation of 5-HT1A- or 5-HT1c-receptors. CGS 12066B attenuated the head shake response but only at 10mg kg- '. 5. The results suggest that interactions exist between the different 5-HT receptor subtype-mediated events. Therefore, care is needed in drawing conclusions from functional measurements when compounds have more or less equal affinities for more than one 5-HT-receptor subtype.
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PMID:Behavioural evidence for functional interactions between 5-HT-receptor subtypes in rats and mice. 215 Jan 80

The role of the 5-hydroxytryptamine (5-HT) receptor subtypes in the spinal cord in the regulation of nociception is unknown. This study examined whether administration of different 5-HT1 receptor agonists into the spinal subarachnoid space of mice modulates the nociceptive tail-flick reflex, and whether effects on the tail-flick reflex involve changes in tail skin temperature. The tail-flick latencies (the time needed to evoke the tail-flick reflex by noxious radiant heat) were significantly increased after intrathecal (i. th.) injection of 5-HT (10-20 micrograms), the 5-HT1A/5-HT1B receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 10-20 micrograms), the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 20 micrograms) and after i.th. injection of 1(m-chlorophenyl)piperazine (mCPP, 5-20 micrograms) and 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969, 5-20 micrograms) which have high affinity for the 5-HT1B receptors. None of the 5-HT1 receptor agonists had the ability to change the tail skin temperature. The results show that in the mouse i.th. injection of both 5-HT1A and 5-HT1B receptor agonists has the ability to inhibit the tail-flick reflex without interfering with the tail skin temperature.
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PMID:The role of spinal cord 5-HT1A and 5-HT1B receptors in the modulation of a spinal nociceptive reflex. 215 Jul 69

1. Phorbol esters are known to inhibit phospholipase C-mediated hydrolysis of membrane phosphoinositide. This inhibition is attributed to participation of protein kinase C (PKC) in a negative-feedback control of phosphoinositide metabolism. We have tested this hypothesis by using different types of activators and inhibitors of PKC. 2. Phorbol-12,13-dibutyrate (PDB) inhibited the stimulatory effect of acetylcholine (ACh) on [3H]inositol monophosphate ([3H]IP) formation in cultured sympathetic neurons of the chick embryo and adrenal medulla of the rat. 3. Acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) activated neuronal PKC by 3- to 8-fold. The extent of PKC activation by 100 microM-ACh was comparable to that of 100 nM-PDB. Activation of PKC by pre-incubation of sympathetic neurons with ACh (or 5-HT) did not inhibit the stimulatory effects of ACh (or 5-HT) on [3H]IP formation. 4. Pre-treatment of sympathetic neurons or adrenal medulla with a PKC inhibitor H7 (1-(5-isoquinolinyl-sulphonyl)-2-methyl-piperazine) almost completely blocked activation of the enzyme induced by PDB, ACh or 5-HT. However, blockade of PKC did not prevent the inhibitory effects of PDB on ACh-induced [3H]IP formation. 5. Vasoactive intestinal polypeptide (VIP) and muscarine induced catecholamine secretion from the perfused adrenal medulla via formation of inositol-1,4,5-tirisphosphate (IP3). Phorbol-12,13-dibutyrate decreased muscarine-induced catecholamine secretion. However, activation of PKC by VIP had no effect on muscarine-induced catecholamine secretion and vice versa. 6. These results suggest that PKC is not negatively coupled to phosphoinositide hydrolysis in sympathetic neurons and chromaffin cells. Phorbol esters must have targets other than PKC to interfere with the phosphoinositide hydrolysis.
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PMID:Phosphoinositide hydrolysis is not negatively regulated by protein kinase C in the peripheral tissues of rat and chick. 217 Jun 29

Responses to serotonergic agonists were studied in isolated umbilical arteries obtained from fetal lambs within 2 weeks of term. The order of potency of the agonists was determined to be 2,5-dimethoxy-4-methyl-amphetamine (DOM) greater than 5-hydroxytryptamine (5-HT) greater than alpha-methyl-5-HT greater than 1-(3-chlorophenyl) piperazine = m-trifluoromethyl-phenylpiperazine greater than 8-hydroxy-dipropylaminotetralin greater than 2-methyl-5-HT greater than 1-(2-methoxyphenyl) piperazine. Variations in the sensitivity and potency of the agonists results primarily from the variation in the affinity for the 5-HT2 receptor and less so in the efficacy, alpha-Methyl-5-HT was a full agonist compared to 5-HT. The others were partial agonists. The mean KA values for 5-HT and DOM were 4.71 +/- 0.62 x 10(-7) and 0.36 +/- 0.04 x 10(-7) M, respectively. Contractions to 5-HT and DOM were antagonized by ketanserin with pA2 values being 9.4 and 9.1, respectively, suggesting that they act on the same receptor and that their responses are mediated by 5-HT2 receptors. Contractile responses to 8-hydroxy-dipropylaminotetralin, 2-methyl-5-HT and the phenylpiperazines [m-trifluoromethyl-phenylpiperazine and 1-(3-chlorophenyl) piperazine] were also blocked by ketanserin (10(-8) M), indicating that contractions produced by these agonists were mediated by 5-HT2 receptors. No antagonism by MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) of responses to 5-HT indicates that 5-HT3 receptors are not present in this tissue.
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PMID:Characterization of serotonergic receptors mediating contraction of ovine umbilical artery. 221 59

The actions of 5-hydroxytryptamine (5-HT) on the electrically induced twitch responses of mouse vas deferens were studied. 5-HT at the concentration range of 10(-8) to 10(-4) M produced a "bell-shaped" concentration-response curve on the field-stimulated twitch contractions; the enhancement of the contractions was maximum at 10(-5) M and progressively reduced at the concentrations of more than 10(-5) M. In the presence of ketanserin, whereas the stimulatory response to low concentrations of 5-HT (less than or equal to 10(-6) M) was not changed, that to high concentrations was reversed. The stimulation by 5-HT (less than or equal to 10(-5) M) was principally antagonized by MDL 72222. In the presence of both MDL 72222 and ketanserin, 5-HT inhibited the twitch contractions in a dose-dependent manner. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and BP-554 (1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine), selective 5-HT1A agonists, only inhibited the twitch contractions. Downward slope of the contraction-response curve of 5-HT (greater than or equal to 10(-5) 5 M) was shifted to right in the presence of 8-OH-DPAT. 5-HT and 8-OH-DPAT had no effect on the tension of unstimulated organs. Contractions elicited by ATP were potentiated by 5-HT, which was antagonized by ketanserin. 8-OH-DAPT did not affect ATP-elicited contractions. These results suggest the presence of presynaptic 5-HT1, maybe 5-HT1A and 5-HT3 receptors mediating inhibition and potentiation, respectively, of neurotransmitter release and of postsynaptic responsible for enhancing neurogenic contractions in mouse vas deferens.
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PMID:5-Hydroxytryptamine modulation of electrically induced twitch responses of mouse vas deferens: involvement of multiple 5-hydroxytryptamine receptors. 239 4

Gepirone (BMY 13805), a buspirone analog, was used to determine the antianxiety mechanism of the arylpiperazine class of drugs. Because of the weak effects of these drugs on conflict behavior, isolation-induced aggressive mice were used as the antianxiety model. Gepirone, like buspirone, potently inhibited attacks against group housed intruder mice (ED50 = 4.5 mg/kg i.p.) without causing sedation or ataxia. Inhibition of aggression was potentiated by co-administration of 0.25 mg/kg methiothepin or 2.5 mg/kg methysergide. Gepirone had variable effects on dopamine metabolism and reduced 5-hydroxytryptamine (5HT) metabolism about one third after a dose of 2.5 mg/kg. In contrast to buspirone, which markedly increased dopaminergic impulse flow, gepirone inhibited the firing of most cells recorded from the substantia nigra zona compacta in doses of 2.3-10 mg/kg i.v. and the effects were reversible by administration of haloperidol. The common metabolite of buspirone and gepirone, 1-(2-pyrimidinyl)-piperazine, caused increased firing rates only. Gepirone potently inhibited serotonergic impulse flow recorded from the dorsal raphe nucleus (88.3% after 0.04 mg/kg) and this effect was partially reversed by serotonergic antagonists. Both buspirone and gepirone displaced [3H]-5HT from the 5HT1a binding site in the hippocampus with IC50 values of 10 and 58 nM, respectively. Non-alkyl substituted aryl-piperazines displaced [3H]-5HT from both 5HT1a and 5HT1b binding sites. Thus, although gepirone may be a weak postsynaptic 5HT agonist, its primary effect is to decrease 5HT neurotransmission. In support of this conclusion was the observed potentiation of antiaggressive effects by blocking 5HT receptors wit small doses of methiothepin or methysergide, which would exacerbate the decreased release of 5HT caused by gepirone. These results are in harmony with reports that decreased serotonergic activity has anxiolytic-like effects in animal models of anxiety.
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PMID:Effects of gepirone, an aryl-piperazine anxiolytic drug, on aggressive behavior and brain monoaminergic neurotransmission. 243 24

1. An intracerebral perfusion method, brain microdialysis, was used to assess changes of 5-hydroxytryptamine (5-HT) release in the ventral hippocampus of the chloral hydrate-anaesthetized rat in response to systemic administration of a variety of 5-HT1 receptor agonists. 2. A stable output of reliably detectable endogenous 5-HT was measured in dialysates collected from ventral hippocampus with the 5-HT reuptake inhibitor, citalopram, present in the perfusion medium. 3. Under these conditions the putative 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) caused a dose-dependent (5-250 micrograms kg-1, s.c.) reduction of 5-HT in hippocampal dialysates. 4. Similarly, the putative 5-HT1A agonists gepirone (5 mg kg-1, s.c.), ipsapirone (5 mg kg-1, s.c.) and buspirone (5 mg kg-1, s.c.) markedly reduced levels of 5-HT in hippocampal perfusates whereas their common metabolite 1-(2-pyrimidinyl) piperazine (5 mg kg-1, s.c.), which does not bind to central 5-HT1A recognition sites, had no effect. 5. 5-Methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969), a drug with reported high affinity for brain 5-HT1B binding sites, also produced a dose-dependent (0.25-5 mg kg-1, s.c.) decrease of hippocampal 5-HT output. 6. These data are direct biochemical evidence that systemically administered putative 5-HT1A and 5-HT1B agonists markedly inhibit 5-HT release in rat ventral hippocampus in vivo.
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PMID:5-HT1 agonists reduce 5-hydroxytryptamine release in rat hippocampus in vivo as determined by brain microdialysis. 246 16

Intracellular recordings were made from rat locus ceruleus neurons in the slice preparation in vitro. Depolarizing synaptic potentials (DSP)2 elicited by electrical stimulation were typically 10 to 15 mV in amplitude and 200 msec in duration. Superfusion with 5-hydroxytryptamine (5-HT, serotonin) or the 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT), produced an inhibition of the DSP. The maximal inhibition was 55 +/- 2% (mean +/- S.E.M.). The EC50 for 5-CT was 60 nM, whereas for 5-HT it was 12 microM. Cocaine (10 microM) shifted the 5-HT concentration-response curve to the left and the EC50 to 320 nM. 8-Hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT1A receptor ligand, also inhibited the DSP, but only produced about 65% of the maximal 5-CT or 5-HT response (EC50 = 50 nM). A relatively selective 5-HT1B ligand (65-fold 5-HT1B greater than 5-HT1A), 1-(m-trifluoromethyl-phenyl)-piperazine, acted as a full agonist (EC50 = 110 nM). None of these compounds had any effects on the membrane properties of the cell at the doses tested. The response to 8-hydroxy-2-(di-n-propylamino) tetralin was antagonized by pretreatment with the 5-HT1A antagonist spiperone (1 microM). The estimated KD for spiperone was 16 nM. At this same concentration, however, there was no effect on the 5-CT-induced inhibition. The antagonist 4-(3-ter-butyl-amino-2-hydroxy-propoxyl)-indol-2-carbonic acid isopropyl ester (LM 21-009, 100 nM) was found to be a partial agonist producing a 26 +/- 4% inhibition of the DSP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin agonists inhibit synaptic potentials in the rat locus ceruleus in vitro via 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors. 252 17

The effects of a variety of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on behaviour in 5- and 20-day old rat pups have been investigated. Increased locomotion and head-weaving responses were induced in both age groups by 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin; 5-HT1A agonist); 5-MeODMT (5-methoxy-N,N-dimethyltryptamine; 5-HT1) and RU 24969 (5-methoxy-3(1,2,3,6-tetrahydropyrindin-4-yl)-1H-indole; 5-HT1B/5-5HT1A). The putative 5-HT1A-agonist LY165163 (1-2-(4-aminophenyl)ethyl 4-(3-trifluoromethylphenyl)piperazine) also produced hyperactivity in the developing pups. In contrast, locomotion was not affected by buspirone (5-HT1A); mCPP (1-(3-chlorophenyl)piperazine; 5-HT1B/5-HT1C) and DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane; 5-HT2) though buspirone produced a small increase in head-weaving at 5- and 20-days. The full 5-HT syndrome was induced in older animals (but not neonates) by both 8-OH-DPAT and 5-MeODMT. Large doses of buspirone, mCPP and DOI also produced signs of reciprocal forepaw treading and flattened body posture at 20-days. In addition, mCPP induced grooming and stereotyped mouthing, while DOI increased sniffing behaviour in the young rats. Catecholaminergic mechanisms were implicated in the head-weaving and locomotor responses to 8-OH-DPAT and RU 24969, following experiments with a number of monoamine receptor antagonists. Preliminary findings with (-)-pindolol, which was high affinity for 5-HT1-receptors, suggested that this subtype of receptor may play a role in hyperlocomotion induced by RU 24969.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavioural profiles of putative 5-hydroxytryptamine receptor agonists and antagonists in developing rats. 252 30


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