PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Piperazines”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed1976

Utilization of an enantiomer as a solution to a pharmaceutical problem: application to solubilization of 1,2-di(4-piperazine-2,6-dione)propane.

An enantiomer of the cytotoxic agent (+/-)-1,2-di(4-piperazine-2,6-dione)propane [(+/-)-I] (ICRF 159) was utilized to overcome a solubility problem in the preparation of a solution suitable for intravenous use. The enantiomers were about five times more soluble and melted at about 40 degrees lower than the racemic compound. This study appears to be the first reported instance in which the difference in the physical properties of a racemic compound and its enantiomers was utilized to improve a pharmaceutical formulation. The expected differences in the physical properties of racemic solids and their corresponding enantiomers are discussed briefly in relation to the three racemic modifications known to exist.

Chemistry, Pharmaceutical↗
PubMed1981

Utility of chloranil in assay of naphazoline, clemizole, penicillin G sodium, and piperazine.

A simple and sensitive spectrophotometric method is described for the assay of naphazoline, clemizole, penicillin G sodium, and piperazine. The method was based on the formation of a charge transfer complex between these drugs as n-donors and chloranil, the pi-acceptor. Conformity to Beer's law enabled the assay of dosage forms of these drugs. Compared with official methods, the results obtained were of equal accuracy. A more detailed investigation of th naphazoline-chloranil complex was made with respect to its composition, association constant, and free energy change.

Benzimidazoles↗
PubMed1994

In vivo binding of [123I]4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)- p-iodobenzamido-]ethyl-piperazine, p-MPPI, to 5-HT1A receptors in rat brain.

The in vivo regional distribution and pharmacological profile of a novel iodinated phenylpiperazine derivative, [123I]p-MPPI (4-(2'-methoxy-)phenyl-1-[2'-(N-2"pyridinyl)-p-iodobenzamido-]ethy l- piperazine), in the rat brain were evaluated for use as a potential in vivo imaging agent for 5-HT1A receptors. The new ligand penetrated the blood-brain barrier quickly and efficiently, with 1.2% of the injected dose found in the whole brain at 2 min post i.v. injection. The rate of radioactivity washout was slowest from the hippocampal region, followed by the hypothalamus, cortex, striatum, and cerebellum. The maximum ratio of hippocampus/cerebellum was 3.3 at 30 min postinjection. The specific binding of the radioligand in the hippocampal region, an area rich in 5-HT1A receptor density, was blocked by pretreatment with a dose of (+/-) 8-OH-DPAT (2 mg/kg, i.v.) or WAY 100635 (1 mg/kg, i.v.), whereas the regional distribution of [123I]p-MPPI was unaffected by pretreatment with non-5-HT1A agents such as ketanserin or haloperidol. Ex vivo autoradiographic studies further confirmed that the specific binding of [125I]p-MPPI is associated with 5-HT1A receptor sites. These results indicate that [123I]p-MPPI may be a useful candidate for noninvasive single photon emission computed tomography (SPECT) imaging of 5-HT1A receptor sites in the living human brain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Computer-aided structure-affinity relationships in a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives binding to the mu-opioid receptor.

Molecular modeling studies were carried out on a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives with the aim to highlight the main factors modulating their affinity for the mu-opioid receptor. Structure-affinity relationships were developed with the aid of molecular mechanics and semiempirical quantum-mechanics methods. According to our proposed pharmacodynamic model, the binding to the mu-receptor is promoted by the following physico-chemical features: the presence of hydrocarbon fragments on the nitrogen ring frame capable of interacting with one of two hypothesized hydrophobic receptor pockets; a 'correct' orientation of an N-propionyl side chain so as to avoid a sterically hindered region of the receptor; the possibility of accepting a hydrogen bond from a receptor site complementary to the morphine phenol oxygen.

Bridged Bicyclo Compounds↗
PubMed1995

In vitro and in vivo activity of 1-(1-naphthyl)piperazine at terminal 5-HT autoreceptors in guinea-pig brain.

The effect of 1-(1-naphthyl)piperazine (NP) on the 5-HT terminal autoreceptor modulating 5-HT release was investigated in vitro and in vivo. In vitro 5-HT release was measured in slices of guinea-pig substantia nigra and hypothalamus prelabelled with 3H-5-HT, superfused with Krebs solution and depolarized electrically. NP, at 0.1 and 1 mumol/l, did not modify the calcium-dependent release of 3H-5-HT elicited by electrical stimulation using a frequency of 5 Hz, however at 0.1 mumol/l NP shifted to the right the inhibition curve of the non-selective autoreceptor agonist, 5-carboxamidotryptamine, in both regions. In hypothalamus when using lower frequencies (1 Hz or 0.2 Hz) or under pseudo-one-pulse stimulation, NP decreased the release of 3H-5-HT at 1 mumol/l. In vivo microdialysis was used to measure extracellular levels of endogenous 5-HT in the substantia nigra of freely moving guinea-pigs. The endogenous release of 5-HT was tetrodotoxin (TTX)-sensitive, indicating a neuronal origin of this efflux. NP, administered through the microdialysis probe (1-100 mumol/l), increased the levels of extracellular 5-HT in concentration-dependent and TTX-sensitive manner. These results suggest that in vitro NP acts as a 5-HT autoreceptor partial (ant)agonist in the substantia nigra and hypothalamus of guinea-pigs, and as a full antagonist in vivo. However, NP administered systemically at 10 mg/kg i.p., did not modify the levels of extracellular 5-HT in the substantia nigra. This lack of systemic effect of NP probably results from its interaction at other receptors that modify 5-HT neurotransmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effects of repeated administration of the monoamine oxidase inhibitor phenelzine on the discriminability of d-lysergic acid diethylamide (LSD) and 1-(m-trifluoromethylphenyl) piperazine (TFMPP).

Rats trained to discriminate d-lysergic acid diethylamide (LSD; 0.08 mg/kg) or 1-(m-trifluoromethylphenyl) piperazine (TFMPP; 0.8 mg/kg) were treated with the monoamine oxidase inhibitor (MAOI) phenelzine (10 mg/kg/day) for 7 days. After a 24 h "washout" period, they were challenged with the training drug (and dose) or saline, during extinction test sessions. Following 0.08 mg/kg LSD, LSD-trained rats responded primarily on the saline lever (29% drug-appropriate responding) while, after TFMPP (0.8 mg/kg), TFMPP-trained animals responded on the drug lever (75% drug-appropriate responding). These preliminary data suggest that, if serotonin receptors are involved in the behavioral effects of TFMPP, these receptors differ from those involved in the effects of LSD.

Animals↗
PubMed1992

Effects of 3,N,N'-trimethyl-2-phenyl-1,4-piperazine diastereomers on monoamine uptake and monoamine oxidase in rat brain.

The diastereomers of 3,N,N'-trimethyl-2-phenyl-1,4-piperazine dihydrochloride (TPP) were tested for their effects on NA, DA and 5-HT uptake in synaptosomes prepared from hypothalamus, corpus striatum, and frontal cortex, respectively. The diastereomers differed with respect to their inhibitory properties. (2 R, 3 R)-TPP was more potent than the other diastereomers on NA and DA uptake, whereas (2 S, 3 S)-TPP was least potent. In contrast, the (2 S, 3 S)- and (2 S, 3 R)-diastereomers of TPP were more potent than (2 R, 3 R)- and (2 R, 3 S)-TPP as inhibitors of 5-HT uptake. None of the diastereomers affected monoamine oxidase activity. The findings show that the diastereomers of TPP interact stereoselectively with neuronal mechanisms for monoamine uptake, and that the (S)-configuration at the 2 carbon is important for inhibitory actions of TPP on 5-HT uptake.

Animals↗
PubMed1990

Anxiogenic-like effect of infusing 1-(3-chlorophenyl) piperazine (mCPP) into the hippocampus.

1-(3-Chlorophenyl) piperazine (mCPP) was previously shown to have an anxiogenic-like effect, i.e., it decreased total interaction in a rat social interaction test. Evidence indicated mediation by activation of 5-HT1C receptors with an ED50 of approximately 500 micrograms/kg IP (Kennett et al. 1989). A comparable effect is now shown on infusing 4 micrograms of the drug ICV or infusing 0.5 microgram into the hippocampus. Both responses were dose dependent. Infusion of 1 microgram mCPP into the amygdala had no effect. None of the above treatments significantly reduced locomotion. Results are consistent with the postulated role of the hippocampus in anxiety.

Amygdala↗
PubMedDate not supplied

Metabolism of 4-(3-cyclohexylpropionyl)-1-(2-ethoxyphenyl) piperazine (D-16120) by rat liver microsomes.

The metabolic fate of central analgesic 4-(3-cyclohexylpropionyl)-1-(2-ethoxyphenyl) piperazine (D-16120), was studied in vitro with phenobarbital 3-methylcholanthrene and clofibrate induced rat liver microsomal fractions. The presence of four metabolites was directly or indirectly established. Biotransformation products were isolated by TLC and HPLC techniques and, when possible, the structures were confirmed through comparison with synthetic samples. The metabolic pathways involved are oxidative dealkylation, aromatic and alicyclic hydroxylation.

Analgesics↗
PubMed2006

Hierarchical clustering analysis of flexible GBR 12909 dialkyl piperazine and piperidine analogs.

Pharmacophore modeling of large, drug-like molecules, such as the dopamine reuptake inhibitor GBR 12909, is complicated by their flexibility. A comprehensive hierarchical clustering study of two GBR 12909 analogs was performed to identify representative conformers for input to three-dimensional quantitative structure-activity relationship studies of closely-related analogs. Two data sets of more than 700 conformers each produced by random search conformational analysis of a piperazine and a piperidine GBR 12909 analog were studied. Several clustering studies were carried out based on different feature sets that include the important pharmacophore elements. The distance maps, the plot of the effective number of clusters versus actual number of clusters, and the novel derived clustering statistic, percentage change in the effective number of clusters, were shown to be useful in determining the appropriate clustering level. Six clusters were chosen for each analog, each representing a different region of the torsional angle space that determines the relative orientation of the pharmacophore elements. Conformers of each cluster that are representative of these regions were identified and compared for each analog. This study illustrates the utility of using hierarchical clustering for the classification of conformers of highly flexible molecules in terms of the three-dimensional spatial orientation of key pharmacophore elements.

Cluster Analysis↗
PubMed1989

1-(m-chlorophenyl)piperazine (mCPP) interactions with neurotransmitter receptors in the human brain.

The affinity of 1-(m-chlorophenyl)piperazine (mCPP) for 11 neurotransmitter receptor binding sites was determined in human brain membranes. mCPP is essentially equipotent at all 5-hydroxytryptamine (5-HT) receptor subtypes (IC50 values ranging from 360 to 1300 nM). The drug displays similar affinity (IC50 = 570 nM for alpha 2-adrenergic receptors labeled for 3H-rauwolscine. mCPP is less potent at alpha 1- and beta-adrenergic, dopamine, and muscarinic cholinergic receptors (IC50 values 2500-24,000 nM). mCPP is inactive at both benzodiazepine receptors and the 5-HT uptake sites at concentrations below 100,000 nM. These data demonstrate that mCPP displays similar potency for multiple neurotransmitter receptor binding sites in human brain.

Adult↗
PubMed1989

Suppression of auditory nerve activity in the guinea pig cochlea by 1-(p-bromobenzoyl)-piperazine-2,3-dicarboxylic acid.

1-(p-Bromobenzoyl)-piperazine-2,3-dicarboxylic acid (pBB-PzDA; 0.03-5 mM), an excitatory amino acid antagonist, was perfused through the guinea pig cochlea while monitoring various cochlear potentials. pBB-PzDA (1-5 mM) reversibly suppressed the amplitude of the compound action potential of the auditory nerve (CAP) and increased the latency of N1 (the first negative wave of the CAP) at all sound intensities. pBB-PzDA had no detectable effect on N1 latency at CAP threshold or presynaptic potentials such as the cochlear microphonics and the summating potential. At the single-cell level pBB-PzDA (5 mM) reversibly suppressed the firing of single auditory nerve ganglion cells. pBB-PzDA appeared to have the same potency in the cochlea as kynurenic acid. We conclude that the mechanism of action of pBB-PzDA is consistent with an antagonism of the hair-cell transmitter at the afferent auditory nerve.

Acoustic Stimulation↗
PubMed1995

The effect of chronic treatment with a novel aryl-piperazine antipsychotic on monoamine receptors in rat brain.

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.

Animals↗
PubMed1985

N-(3-acetylaminophenyl)piperazine hydrochloride (BEA 1654), a putative 5-HT1 agonist, causes constriction of arteriovenous anastomoses and dilatation of arterioles.

Using 3H-ligands and radioactive microspheres we studied the binding characteristics and the effects on the distribution of carotid arterial blood flow of n-(3-acetylaminophenyl)piperazine hydrochloride (BEA 1654). The compound had a Ki value of 32 nM (5-HT: 8 nM) on 5-HT1 but no or very weak affinity for 5-HT2, alpha 1- and alpha 2-adrenoceptor sites in rat cerebral cortex homogenates. Intracarotid infusions of BEA 1654 (0.1-1.0 mg X kg-1 X min-1) were nearly equieffective in untreated and treated (phentolamine plus ketanserin) pigs in redistributing carotid arterial blood towards the nutrient compartment (particularly the skin and ears) at the expense of shunting via arteriovenous anastomoses (AVAs). In view of the high and selective affinity of BEA 1654 to 5-HT1 binding sites, the similarity of pharmacological responses between 5-HT and BEA 1654, and the ineffectiveness of antagonists of 5-HT2 and alpha-adrenergic receptors to block the AVA constriction and arteriolar dilatation caused by both 5-HT and BEA 1654, we conclude that these effects are mediated by 5-HT1 receptors. The vast difference between the ratios of Ki values for 5-HT1 binding sites and of the pharmacologically effective doses of BEA 1654 and 5-HT suggests that either BEA 1654 may be a partial agonist of 5-HT1 receptors or, while the drug binds with both subsets of 5-HT1 receptors, it is only one type which mediates the pharmacological response.

Animals↗
PubMed1987

Pharmacological evidence for the involvement of 1-(2-pyridinyl)-piperazine (1-PmP) in the interaction of buspirone or gepirone with noradrenergic systems.

We investigated in mice the effects of one of the principal metabolites of buspirone and gepirone, 1-(2-pyridinyl)-piperazine (1-PmP), on hypothermia and reduced locomotion induced by clonidine (0.25 and 0.06 mg/kg, respectively), tests related to brain alpha-adrenergic function. Both effects were antagonized dose dependently by 1-PmP (1-16 mg/kg i.p.). Moreover, pretreatment with proadifen (50 mg/kg) prevented the reversal by buspirone and gepirone of clonidine-induced hypothermia. This suggests that 1-PmP could be responsible for some of the apparent noradrenergic effects of buspirone and gepirone.

Animals↗
PubMed1987

Neurochemical and behavioural evidence for an agonist action of 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY 165163) at central 5-HT receptors.

1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY 165163, PAPP) (1 mg/kg s.c.) significantly decreased 5-hydroxytryptophan (5-HTP) accumulation in cortex, hippocampus, striatum, septum, pons + medulla and midbrain and increased DOPA accumulation in the cortex and striatum following inhibition of aromatic amino acid decarboxylase with NSD 1015. LY 165163 increased food intake in non-food-deprived rats over 2, 4 and 24 h after administration. Depletion of brain 5-hydroxytryptamine (5-HT) by parachlorophenylalanine (pCPA) prevented the hyperphagic effect over 2 and 4 h after treatment with LY 165163 (1 mg/kg). Components of the postsynaptically mediated 5-HT behavioural syndrome were not detected at doses of LY 165163 between 1 and 10 mg/kg, although locomotion was increased at lower doses and the rats were inactive at the highest dose. Results in general indicate that LY 165163 is a centrally active agonist at 5-HT presynaptic receptors.

5-Hydroxytryptophan↗
PubMed1989

Agonist activity of a novel compound, 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554), at central 5-HT1A receptors.

We used an in vitro radioligand receptor binding assay with rat cerebral cortex, hippocampus and striatum membrane preparations to show that 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554) had much higher affinity for 5-HT1A recognition sites than for 5-HT1-non-A, 5-HT2, benzodiazepine, dopamine D-2 and alpha 2-adrenergic recognition sites. The compound inhibited the activity of forskolin-stimulated adenylate cyclase in rat hippocampal membranes. Intraperitoneal injection of BP-554 to mice decreased the concentration of only 5-hydroxy-indoleacetic acid of the amines and their metabolites in the brain and decreased the accumulation of 5-hydroxytryptophan in the brain after decarboxylase inhibition by 3-hydroxybenzylhydrazine. Furthermore, the administration of BP-554 caused hypothermia and increased serum corticosterone levels in mice. The observed effects of BP-554 were similar to those of 8-hydroxy-2-(di-n-propylamino)tetralin. These results suggest that BP-554 acts as a selective 5-HT1A receptor agonist in vivo.

8-Hydroxy-2-(di-n-propylamino)tetralin↗