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At least 307 records · Page 17Linked to original sources

PubMed1986

1-(1-Naphthyl)piperazine, a central serotonin agonist.

1-(1-Naphthyl)piperazine (1-NP) had high affinity for tritiated serotonin, tritiated LSD (lysergic acid diethylamide) and tritiated spiperone binding sites in rat brain cortex in vitro. 1-NP at doses of 3-30 mg/kg i.p. decreased 5-hydroxyindoleacetic acid (5-HIAA) concentration in whole brain of rats in vivo. The 30 mg/kg dose caused a significant increase in serum corticosterone concentration. At doses of 3-30 mg/kg i.p., 1-NP reduced the accumulation of 5-hydroxytryptophan following decarboxylase inhibition by NSD 1015 in rat hypothalamus and striatum. Reduced serotonin turnover and elevated serum corticosterone concentrations are interpreted as evidence of central serotonin receptor activation by compounds of this structural class. 1-NP has previously been reported to antagonize vascular serotonin receptors, suggesting that it, like 1-(m-trifluoromethylphenyl)piperazine, behaves as an antagonist at peripheral (vascular) serotonin receptors despite being an agonist at central serotonin receptors.

Animals↗

PubMed1988

Resolution and pharmacological properties of the enantiomers of the potent alpha-adrenoceptor antagonist 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine.

Resolution of the optical isomers of the alpha-adrenoceptor antagonist IP-66 (1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine) and its intermediate IP-30 (1-[2-hydroxy-2-(3'-pyridyl)ethyl]-4- (2'-methoxy-phenyl)piperazine have been carried out. Optical purity was assayed by high-pressure liquid chromatography. The antagonistic potencies of racemic mixtures and stereoisomers toward phenylephrine- and norepinephrine-induced contraction in isolated rat aortic strips have been compared. (+)-IP-66 and (+)-IP-30 were resp. 363 and 170 times more potent than respective (-) isomers in eliciting competitive alpha 1-adrenoceptor blockade. Similarly IP-66 (+) or (+/-) were extremely more effective than the (-) isomer in antagonizing norepinephrine-induced pressor responses in pithed rat.

Adrenergic alpha-Antagonists↗

PubMed1987

Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5-HT-2 and 5-HT-1c) receptors.

Serotonin (5-HT)-stimulated phosphoinositide hydrolysis is mediated by the 5-HT-2 receptor in rat cerebral cortex and by the 5-HT-1c receptor in rat choroid plexus. These systems were used to determine relative efficacies of piperazine derivatives at the 5-HT-2 and 5-HT-1c receptors. Both quipazine and 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) stimulated phosphoinositide hydrolysis in cerebral cortex, and these effects were blocked by ketanserin. The maximum responses to these agonists were 80% of the maximum response to 5-HT. m-Trifluoromethylphenylpiperazine (TFMPP), m-chlorophenylpiperazine (MCPP) and 1-(1-naphthyl)-piperazine (1-NP) did not stimulate phosphoinositide hydrolysis in cerebral cortex at concentrations that blocked the effect of 5-HT. In the choroid plexus, TFMPP and MCPP, as well as MK-212 and quipazine, increased phosphoinositide hydrolysis and mianserin blocked these effects. MK-212 had an efficacy which was equal to that of 5-HT, whereas quipazine, MCPP and TFMPP were partial agonists in the choroid plexus. 1-NP did not stimulate phosphoinositide hydrolysis in choroid plexus but completely blocked the effect 5-HT. On the basis of these data, we conclude that quipazine and MK-212 are partial agonists at 5-HT-2 receptors in cerebral cortex, whereas 1-NP, TFMPP and MCPP are pure antagonists of the cortical 5-HT-2 receptor. However, TFMPP and MCPP as well as quipazine and MK-212 are agonists at the 5-HT-1c receptor, while 1-NP is a pure antagonist of the 5-HT-1c receptor in choroid plexus.

Animals↗

PubMedDate not supplied

Synthesis of asymmetric 1,4-disubstituted piperazines and their psychotropic and cardiovascular actions. Part II.

New asymmetric piperazines 9-19 were obtained by condensation of 1-acyl-piperazines with 1,2-epoxy-3-chloropropane, arylacid chlorides, phenols, amines and 1-(alpha-naphthyloxy)-2,3-epoxypropane. Most of the compounds produced a transient hypotension and exerted a spasmolytic action of the isolated intestine. Compounds 10, 11 and 13 displayed a weak antiarrhythmic effect in the adrenaline arrhythmia test in rats. Compounds 14 and 15 increased the coronary flow, but their action was weaker than that of compound 4, described in the first part of the paper.

Animals↗

PubMedDate not supplied

Analysis of piperazine drug formulations for N-nitrosamines.

A quantitative method is described for the measurement of N-mononitrosopiperazine (NPIP) and N,N'-dinitrosopiperazine (DNPIP) in drug formulations containing piperazine, using a gas chromatograph interfaced to a thermal energy analyzer (GC/TEA). The method has detection limits of 20 ppb for NPIP and 12 ppb for DNPIP. In a survey of 6 products available on the Canadian market, all contained NPIP at levels of 0.38-15.3 micrograms NPIP/g piperazine and none contained any detectable amount of DNPIP.

Chromatography, Gas↗

PubMed1985

Evaluation of febantel used concurrently with piperazine citrate in horses.

Fifty horses from a herd known to have benzimidazole-resistant small strongyles were treated with febantel (6 mg/kg), combinations of febantel (6 mg/kg) and piperazine citrate (25 or 55 mg base/kg), thiabendazole (44 mg/kg), or placebo (0.6 ml of water/kg). Pretreatment and 7-day posttreatment fecal examinations were done. Fecal cultures, strongyle egg per gram (epg) counts, sugar flotation fecal examinations, and in vitro testing for benzimidazole resistance were performed. Results of fecal examinations before treatment were similar in all horses, and results of testing were positive for benzimidazole resistance. Horses treated with febantel and piperazine at all dosages had significantly lower mean strongyle epg counts and greater percentage reduction in mean strongyle epg counts (99.7% to 99.9%) 7 days after treatment, compared with those determined for horses treated with febantel, thiabendazole, or placebo. Adverse reactions to treatment were not observed.

Animals↗

PubMed1979

Spectrophotometric determination of piperazine and its salts in pharmaceuticals.

A spectrophotometric determination of piperazine and some of its salts is described. The method depends on the UV measurement of the N-nitroso derivatives formed by the interaction of piperazine with nitrous acid. The chromophore is developed by heating the reaction mixture at 80 degrees C for 15 min, at pH 2.3--2.6. Beer's law is obeyed in the range 1--15 micrograms/mL.

Dosage Forms↗

PubMedDate not supplied

Synthesis and effect of asymmetric 1,4-bis(aminoacyl) piperazines on neuromuscular transmission.

The condensation of asymmetrically substituted 1,4-bis(haloacyl) piperazines with secondary amines yielded asymmetric 1,4-bis (aminoacyl) piperazines 3-6, which were further transformed into the respective dimethiodides 3b-6b by treatment with methyl iodide. Those compounds were found to inhibit the neuromuscular transmission by blocking the motor end-plate receptors. Compounds containing piperidine moiety and branched acyl chain 4b displayed enhanced activity.

Acetylcholine↗

PubMed1984

Effects of piperazine citrate and of the anti-Ascaris fraction of the ethanolic extract of the bark of Polyadoa umbellata (erin) on mammalian non-vascular smooth muscle.

At 500 micrograms-4 mg/ml piperazine and the anti-Ascaris fraction of the ethanolic extract of the bark of the erin tree (Polyadoa umbelleta) have equipotent inhibitory effects on submaximal contractions induced by equipotent doses of acetylcholine, nicotine and 5-hydroxytryptamine on the guinea-pig ileum and the rabbit duodenum. Similar inhibitory effects were noted on: acetylcholine, adrenaline, histamine, and barium chloride-induced contractions in the guinea-pig vas deferens, oxytocin and acetylcholine-induced contractions in the non-pregnant rat uterus. These actions indicate that piperazine and erin possess definite non-specific smooth muscle depressant properties. The need for the elucidation of the chemical nature of the active constituent in "erin" and for in-vivo anti-Ascaris activity studies in man is stressed.

Acetylcholine↗

PubMedDate not supplied

[The mechanisms of the anxiolytic action of 1-(2-pyrimidinyl)-piperazine derivatives, serotonin agonists].

1-(2-pyrimidinyl)-piperazine derivatives (ipsapirone and campirone) injected intraperitoneally or into dorsalis nucleus raphe and dorsalis hippocampus of rats revealed dose-dependent anxiolytic action in avoidance procedure and conflict situations. 5-HT locally injected into the nucleus raphe and hippocampus revealed a role of serotoninergic mechanisms of these brain formations in the studied anxiety conditions of different aversive genesis. It is concluded that anxiolytic effect dissociation revealed in different anxiety tests, are stipulated by serotonin and its agonists due to nucleus raphe and hippocampus chemical stimulation my suggest their different neurochemical contribution and nonserotoninergic component involved in the mechanism of 1-(2-pyrimidinyl)-piperazine derivative anxiolytic action.

Animals↗

PubMed1976

Indirect chelatometric determination of piperazine in some pharmaceutical preparations.

An indirect complexometric method is described for the determination of piperazine alone or in its pharmaceutical preparations. The method involves treatment of the aqueous solution of piperazine with carbon disulphide, ammonia solution and a known excess of cupric acetate, filtration of the formed precipitate and determination of the excess cupric acetate with EDTA using PAR as indicator.

Acetates↗

PubMed1977

Biphasic effects of m-chlorophenyl-piperazine on 3,4-dihydroxyphenylacetic acid concentration in rat brain.

m-Chlorophenyl-piperazine dihydrochloride injected i.p. into rats caused a rapid increase and a subsequent decrease in whole brain concentration of 3,4-dihydroxyphenylacetic acid (DOPAC), a metabolite of dopamine. The increase in DOPAC at 30 min and the decrease at 3 hrs were dose-related and occurred after doses as low as 5 mg/kg of m-chlorophenyl-piperazine dihydrochloride.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2004

Does a reinforced kinetic macrocyclic effect exist? the demetallation in strong acid of copper(II) Complexes with open and cyclic tetramines containing a piperazine fragment.

The demetallation in acidic solution of the Cu(II) complexes with open-chain and cyclic tetramines containing a piperazine unit (2 and 3) has been investigated in terms of its kinetic aspects and compared with the behaviour of unsubstituted counterparts (tetramines 1 and 4). The presence of the piperazine fragment slows demetallation of the open-chain-ligand complex owing to the activation barrier associated with the conformational change from boat-to-half-boat; however, it does not affect the demetallation of the macrocyclic complex, which involves the spontaneous boat-to-twist conformational change. Thus, lateral reinforcement of a cyclam-like ligand does not add any further contribution to the typical inertness in demetallation of macrocyclic complexes.

Journal Article↗

PubMed1987

Effects of gepirone, an aryl-piperazine anxiolytic drug, on aggressive behavior and brain monoaminergic neurotransmission.

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.

Aggression↗

PubMed1982

Myoclonus in guniea pigs is induced by indole-containing but not piperazine-containing 5HT agonists.

L-5-Hydroxytryptophan (5HTP) induces in guinea pigs a myoclonic jerking which is dependent upon stimulation of brainstem 5-hydroxytryptamine (5HT) receptors. We have investigated the ability of 5HT precursors and a range of synthetic 5HT agonists to produce myoclonus. The 5HT precursors and 5HT agonists containing an indole nucleus induced dose-dependent jerking in guinea pigs. In contrast, 5HT agonists possessing a piperazine moiety induced occasional jerking only at toxic doses, but not a those doses normally associated with 5HT agonist activity. The difference in activity between the indole-containing compounds and piperazine-containing 5HT agonists suggests that myoclonus is due to activation of an indole-selective brainstem 5HT receptor and provides further evidence for multiple cerebral 5HT receptors.

Animals↗

PubMed1996

NCS-MPP (4-(2'-methoxy-phenyl)-1-[2'-(N-2"-pyridyl)-p-isothiocyanobenz amido]-ethyl-piperazine): a high affinity and irreversible 5-HT1A receptor ligand.

A novel irreversible 5-HT1A receptor binding ligand, NCS-MPP (4-(2'- methoxy-phenyl)-1-[2'-(N-2"-pyridyl)-p-isothiocyanobenzamido]- ethyl-piperazine), based on the new 5-HT1A receptor antagonist p-MPPI (4-(2'-methoxy-phenyl)-1-[2'-(N-2"-pyridyl)-p-iodobenzamido]-ethyl -piperazine ), was synthesized, and its binding characteristics were evaluated using in vitro homogenate binding with rat hippocampal membranes. The Ki value of NCS-MPP was estimated to be 1.8 +_ 0.2 nM using analysis of concentration-dependent inhibition for the binding of [125I]p-MPPI to 5-HT1A receptors. NovaScreen of NCS-MPP showed low to moderate binding affinities to alpha-1, alpha-2-adrenergic and 5-HT2 receptors, with Ki values of 350, 420, and 103 nM, respectively. These data strongly suggest that the ligand bound to 5-HT1A receptors with high affinity and high selectivity. Irreversible inhibition of [125I]p-MPPI binding by NCS-MPP following a 5 min incubation at room temperature was concentration dependent; the inhibition increased to 50% at a concentration less than 10 nM, and became more pronounced (90%) at 400 nM. Under similar assay conditions, NCS-MPP was significantly less efficient in irreversibly inhibiting agonist ligand [125I]8-OH-PIPAT binding to 5-HT1A receptors at lower concentrations (<10nM). After pretreatment of membranes with a low concentration of NCS-MPP (2nM), there was an apparent loss of [125I]p-MPPI binding sites, as expected, but no change in the binding affinity (Kd) was observed. However, the significant increase in Kd at a higher concentration of NCS-MPP (50 nM) indicated that there may be a secondary alkylation site, which may not be directly involved in p-MPPI binding to receptors; nevertheless, it would lead to an increased Kd value. The availability of an irreversible ligand, NCS-MPP, may provide a useful tool for studies of 5-HT1A receptors in the central nervous system.

Animals↗

PubMed1990

Ipsapirone and 1-(2-pyrimidinyl)-piperazine increase rat locus coeruleus noradrenergic activity.

The effects of systemically administered ipsapirone, an aryl-piperazine compound, and its major metabolite 1-(2-pyrimidinyl)-piperazine (1-PP), on locus coeruleus (LC) noradrenergic activity was investigated. On an equimolar basis both ipsapirone and 1-PP were approximately equipotent in increasing LC neuronal activity. However, pretreatment with 1-PP caused a significantly greater parallel shift to the right of the dose response curve for the inhibitory action of the LC alpha 2-receptor agonist clonidine compared to ipsapirone. Biochemically, pretreatment with SKF 525A, a compound which prevents the formation of 1-PP from ipsapirone, diminished the ipsapirone-induced increase in MOPEG-SO4 levels in the brainstem and cortex. These data, together with the findings that 1-PP is more potent than ipsapirone in displacing 3H-clonidine from cerebral cortical membranes, suggest that the parent drug influences LC neuronal activity via the action of I-PP on LC alpha 2-adrenoceptors.

Action Potentials↗

PubMed1992

Simultaneous high-performance liquid chromatographic analysis of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in plasma using electrochemical detection.

A selective and sensitive high-performance liquid chromatographic method with coulometric detection is described for the quantitation of buspirone and its active metabolite, 1-(2-pyrimidinyl)piperazine, in plasma samples of mice treated orally with buspirone (10 mg/kg body weight). The analytes are extracted with a carboxylic acid solid-phase extraction column before chromatography. A dual-electrode electrochemical detector is used. The limit of detection is 50 pg for buspirone and 35 pg for 1-(2-pyrimidinyl)piperazine.

Administration, Oral↗