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 541 records · Page 30Linked to original sources

PubMed2003

A PET study after treatment with an anxiety-provoking agent, m-chlorophenyl-piperazine, in conscious rhesus monkeys.

UNLABELLED: Several PET studies have been performed on conscious nonhuman primates to examine brain function. However, it is unclear how anxiety or stress during PET measurements influences brain function. In the present study, we examined the effects of a well-known anxiety-provoking agent, m-chlorophenyl-piperazine (mCPP), on regional cerebral blood flow (rCBF) and the regional cerebral metabolic rate of glucose (rCMRglc) using PET on conscious rhesus monkeys. METHODS: Male rhesus monkeys with experience undergoing PET measurements were used. Twenty and 40 min after mCPP injection (0.2, 1.0, or 5.0 mg/kg intramuscularly; n = 5), rCBF and rCMRglc were measured using an intravenous injection of (15)O-H(2)O and (18)F-FDG, respectively. Physiologic parameters, plasma cortisol, and prolactin levels were monitored during PET measurements. RESULTS: Treatment with mCPP significantly increased rCBF in both the cingulate cortex and striatum in a dose-dependent manner, and bell-shaped reductions in rCMRglc were observed for all regions examined. mCPP also significantly increased plasma cortisol and prolactin levels. Physiologic parameters were not affected by mCPP treatment. CONCLUSION: The present study demonstrates that treatment with the anxiety-provoking agent mCPP significantly affects rCBF and rCMRglc in conscious monkeys. Therefore, since the increases in hormone levels demonstrate that mCPP treatment produced anxiety or stress, these results suggest that anxiety or stress influences conscious brain function. Furthermore, the present study suggests that prevention of anxiety or stress is important when measuring conscious brain function in monkeys.

Animals↗

PubMed1992

Effects of a novel piperazine derivative (CGP 29030A) on nociceptive dorsal horn neurons in the rat.

In anaesthetized rats and cats, the effects of the piperazine derivative CGP 29030A on the discharges of functionally identified dorsal horn neurons and gamma-motoneurons was studied. The compound exhibited a marked inhibitory action on presumably nociceptive dorsal horn neurons that processed input from high-threshold mechanosensitive receptors in the skin and deep somatic tissues (muscle, tendon, joint). Significant effects were obtained at a dose of 10 mg/kg p.o. and higher; the onset of action was fast (approximately 10 min). In contrast to presumably nociceptive dorsal horn neurons, cells having input from low-threshold mechanosensitive receptors in the skin and deep tissues were not affected by the compound. Thus CGP 29030A has a quite specific action on dorsal horn neurons that probably mediate pain. Systemic effects on the blood pressure and on the activity of sympathetic efferent fibres did not occur. The lack of effect of CGP 29030A on nociceptive neurons in spinalized animals suggests that the site of action is not the segmental spinal cord but the supraspinal CNS. gamma-motoneurons supplying the gastrocnemius-soleus muscle were likewise inhibited by the compound but at a higher dose (equal to and exceeding 30 mg/kg). The data show that CGP 29030A is a compound with marked and specific analgesic action. As it also inhibits gamma-motoneurons, CGP 29030A may be of benefit in the treatment of painful disorders which are complicated by increased motor activity (cramp, spasm).

Action Potentials↗

PubMedDate not supplied

[The serotonin- and dopaminergic mechanisms in the action of 1-pyrimidinyl piperazine derivatives].

It has been established in experiments on spinal ganglia neurons of rats that 1-pyrimidinyl-piperazine derivatives show the properties of partial agonists of 5-HT1A-receptors. Some of them were discovered to be capable of blocking D2-dopamine receptors. Comparison of neuronal and behavioral activity of the substances tested has demonstrated that their anxiolytic activity detectable under the conditions of the conflict situation method significantly correlates with 5-HT1A-mimetic and anti-dopamine activity. The latter one correlates well with the influence of the substances tested on the time of immobilization in the forced swimming test.

Animals↗

PubMed1992

Kinetics, brain uptake, and receptor binding of tandospirone and its metabolite 1-(2-pyrimidinyl)-piperazine.

Tandospirone is an azaspirodecanedione derivative under investigation as an antidepressant. Metabolism of tandospirone in humans and rodents leads to 1-(2-pyrimidinyl)-piperazine (1-PP), presumed to have pharmacologic activity. To determine the relative contributions of tandospirone and 1-PP after tandospirone administration, we evaluated open-field activity, pharmacokinetics, and receptor binding of tandospirone and 1-PP in a mouse model. Tandospirone significantly reduced open-field activity during 30 minutes at doses of 1-20 mg/kg. 1-PP had no significant effect on activity except for a trend toward reduction at 20 mg/kg. At 30 minutes after administration, plasma and cortex concentrations of tandospirone and 1-PP increased in proportion to dose. Plasma protein binding (free fraction) for tandospirone was 30.4%, and for 1-PP, 87.5%. Receptor binding studies indicated that tandospirone bound with high affinity to serotonin1A sites, and with low affinity to serotonin2, alpha 1, alpha 2, and benzodiazepine sites. 1-PP bound with high affinity to alpha 2 sites and with low affinity to the other sites evaluated. A "receptor occupancy index" of tandospirone cortex concentrations divided by receptor affinity suggests that after acute administration of tandospirone, effects are likely to be due to the parent compound rather than to the metabolite. Similar conclusions are likely to be correct for other azaspirodecanediones, including buspirone.

Animals↗

PubMed1979

[Cardiac anti-arrhythmic effect of various N-substituted piperazine derivatives with respect to aconitine in the rat].

Anti-arrhythmic activity of some piperazine derivatives has been investigated upon cardiac arrythmia induced by aconitine in albinos rat. Among mono-substituted derivatives trimetazidine is active. Among di-substituted derivatives cinepazide and hydroxyzine are active but medibazine have a doubtful activity and piribedil and cinnarizine are devoid of activity.

Aconitine↗

PubMedDate not supplied

Study on organic nitrates, part VIII. Pharmacological activity and nitric oxide generation capacity of nitrate derivatives of piperazine.

Organic nitrates, derivatives of piperazine, incubated with L-cysteine hydrochloride in phosphate buffer at appropriately high pH and temperature underwent decomposition, releasing nitric oxide (NO). NO generated in this reaction was quantitated by polarographic method using a selective ISO NO sensor. Spontaneously hypertensive rats were used in the tests of hypotensive activity of both investigated organic nitrates and their hydroxyl analogues. The experiments with both groups of compounds were performed under identical conditions. The results of the study demonstrated that the ability of individual compounds to release NO influenced in a different manner their pharmacological activity. Only the compound which released the largest quantity of NO during in vitro tests exhibited in vivo the most prolonged hypotensive effect and significant decrease in all arterial blood pressure parameters.

Animals↗

PubMed2006

[Metabolites of R, S-1-(2-methoxyphenyl)-4-[3-(naphtha-1-yl-oxy)-2-hydroxypropyl]-piperazin in rat plasma].

AIM: To study the metabolites of R, S-1-(2-methoxypheyl)-4-[3-(naphthal-yl-oxy)-2-hydroxypropyl] -piperazine, (naftopidil, NAF), a novel antihypertensive drug in rat plasma. METHODS: The rat plasma samples were analyzed by LC/MS after oral administration of NAF. According to MS relativity of metabolites and parent compound (NAF) and metabolic rule of compound with similar structure, the structure of potential metabolites were postulated. Phase I metabolites were identified by HPLC/MS and by comparison with authentic standards, phase II conjugates were indirectly identified with beta-D-glucuronidase in presence or absence of glucuronidase selective inhibitor D-saccharric acid beta-1,4-Lactone. RESULTS: Phase I metabolites desmethyl-naftopidil (DMN), (phenyl) hydroxynaftopidil (PHN), (naphthyl) -hydroxy-naftopidil (NHN) were separated and identified in rat plasma by comparison with reference substances, phase II conjugates, NAF and NHN glucuronide conjugates were separated and tentatively identified by hydrolysis with glucuronidase, the aglycones, NAF and NHN, were identified in rat plasma. CONCLUSION: The major metabolic pathway of NAF in rat plasma should be the hydroxylation of the phenyl or nephthyl moiety of NAF and demethylation of NAF. Therefore, (naphthyl) hydroxyl-metabolite and NAF followed by conjugation with beta-glueuronic acid.

Animals↗

PubMed2006

Increased serotonergic functions following adminstration of 1-(1-naphthyl) piperazine in propranolol injected rats.

Propranolol a beta adrenergic antagonist, binds with 5-HT1 receptor. 1-(1-naphthyl) piperazine (1-NP) a derivative of quipazine has serotonin antagonist activity at 5-HT2 and agonist activity at 5-HT1 site. In the present study neurochemical and behavioral effects of 1-NP was monitored in saline and propranolol injected rats. 1NP increased locomotor activity in saline as well as in propranolol injected rats. Administration of propranolol also increased locomotor activity and these increases were more enhanced following 1-NP administration. Levels of 5-HT were not altered following the administration of 1NP in saline as well as propranolol injected rats. 5-HT turnover however decreased by the administration of propranolol Adminstration of 1NP decreased 5-HT turnover in saline but not in propranolol injected rats.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Search for potential amoebicides. Part IV. Some hydrazones derivatives of 2-nitro-4-5-dimethoxybenzhydrazide and of 1-4-bis-[alpha(o-acetylhydrazino) phenethyl] piperazine.

By the condensation of 2-nitro-4-5-dimethoxybenzhydrazide and of 1,4-bis[alpha(O-acetylhydrazino) phenethyl] piperazine with various carbonyl compounds 42 hydrozones were synthesissed. Out of them 26 compounds were tested against the axenic-culture of E. histolytica at conc. of 125 mug/ml but no significant amoebicidal activity was observed.

Amebicides↗

PubMedDate not supplied

[The search for new antiparasitic agents. 8. The synthesis and study of the acute toxicity, anti-alveolar hydatid and antihymenolepiasis activity of 1-alkyl-4[4-(heterylamino)phenyl]piperazines].

The synthesis and the acute toxicity and anticestodal activity of l-alkyl-4-[-(heterylamino)phenyl]-piperazines are presented. These compounds were found to be able to suppress the growth of larvocysts of Echinococcus multilocularis in cotton rats when injected intraperitoneally in a single dose of 0.25 g/kg, close to capacity of mebendazole. The tested compounds were also highly effective against the adult stage of Hymenolepis nana. Experimentally infected mice given an oral single dose of 0.2-0.5 g/kg of the drug were radically cured.

Animals↗

PubMed1977

1,4-Bis-[1-methyl-5-nitroimidazolyl-(2-methyleneimino)]-piperazine, a new drug with marked activity against Entamoeba histolytica. Short communication.

1,4-Bis-[1-methyl-5-nitroimidazolyl-(2-methyleneimino)]-piperazine (HOE 316) administered orally produces an effect which is clearly superior to that of metronidazole against Entamoeba histolytica in the golden hamster and slightly inferior against Trichomonas fetus and T. vaginalis in the mouse. The acute tolerance of the compound is very good (LD 50% greater than 10 g/kg body weight). It is assumed that the possible main metabolite of HOE 316 is a monohydrazone: 1-methyl-2-(4-amino-piperazino-1-imino-methyl)-5-nitroimidazole.

Animals↗

PubMed1986

Central serotonin agonist actions of LY 165163, 1-(m-trifluoromethylphenyl)-4-(p-aminophenylethyl) piperazine, in rats.

1-(m-Trifluoromethylphenyl)-4-(p-aminophenylethyl)piperazine (LY 156163), reported previously to have selective affinity for the 5-HT1A subtype of serotonin receptor in vitro, was studied at doses of 1.25 to 20 mg/kg i.p. in rats to determine if it had properties characteristic of centrally acting serotonin agonists. LY 165163 decreased whole brain concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid, but not of serotonin itself, decreased the rate of accumulation of 5-hydroxyindoleacetic acid after probenecid administration to block its efflux from brain, decreased the rate of decline in serotonin concentration after inhibition of serotonin synthesis with alpha-propyldopacetamide and decreased the accumulation of 5-hydroxytryptophan after decarboxylase inhibition by m-hydroxybenzylhydrazine. LY 165163 also decreased 5-hydroxyindoleacetic acid concentrations in two specific brain regions, striatum and hypothalamus. Serum concentrations of corticosterone and prolactin were increased by doses of LY 165163 that reduced serotonin turnover. These effects are all consistent with evidence from other studies that LY 165163 is a centrally acting serotonin agonist. LY 165163 also increased the concentrations of two dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, measured in whole brain as well as in striatum and hypothalamus, but did not alter dopamine concentration. The accumulation of dopa after decarboxylase inhibition was accelerated by LY 165163. The increases in hormone concentrations in serum and of dopamine metabolite concentrations in brain were not antagonized by pretreatment with metergoline, a serotonin antagonist. The mechanisms of those effects require further study.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1987

Inhibition of human neutrophil chemotaxis by the protein kinase inhibitor, 1-(5-isoquinolinesulfonyl) piperazine.

The protein kinase inhibitor, 1-(5-isoquinolinesulfonyl) piperazine (C-I), inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol, without inhibiting superoxide release from PMN stimulated with the chemoattractants C5a or N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe). In this study, we investigated the effect of C-I on human PMN chemotaxis to C5a, f-Met-Leu-Phe, leukotriene B4 (LTB4), and fluoresceinated N-formyl-methionyl-leucyl-phenylalanine-lysine (f-Met-Leu-Phe-Lys-FITC). PMN, preincubated for 5 min at 37 degrees C with 0 to 200 microM C-I, were tested for their migratory responses to the chemoattractants. C-I (greater than or equal to 1 microM) significantly inhibited PMN chemotaxis to f-Met-Leu-Phe, f-Met-Leu-Phe-Lys-FITC, and C5a without affecting random migration. Maximal inhibition of chemotaxis to these attractants occurred with greater than or equal to 50 microM C-I, at which chemotaxis was inhibited by 80 to 95%. The C-I inhibition was reversible. In contrast, 200 microM C-I did not inhibit the number of PMN migrating to LTB4, although, the leading front of PMN migration to LTB4 was inhibited by C-I. C-I inhibited PMN orientation to C5a and f-Met-Leu-Phe without affecting orientation to LTB4. C-I did not inhibit the binding of radiolabeled f-Met-Leu-Phe or f-Met-Leu-Phe-Lys-FITC to PMN. These findings suggest that the chemotactic responses of PMN to f-Met-Leu-Phe and C5a involve a protein kinase-dependent reaction which is inhibited by C-I.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1987

Behavioural and radioligand analysis of the effect of two new piperazine derivatives with anxiolytic properties.

The experiments were carried out on Wistar rats, using a conflict situation consisting in opposition of two motivations: positive (water drinking) and negative (electrical pain). Two newly-synthesized piperazine derivatives with proved psychotropic activity (4P-183 and GP4) were studied and compared with the classical benzodiazepine tranquilizing agent diazepam. Parallel with this, the affinity of these compounds to the benzodiazepine receptor in mouse brain was tested (radioligand binding of 3H-diazepam), as well as the changes in the characteristics of binding (dissociation constant and density of the receptors) after 14-day administration o doses equal to 1/3 LD50 of the two compounds. The results indicate the existence of anxiolytic (anticonflict) activity in both compounds. The fact that the above-mentioned derivatives do not interact with 3H-diazepam (in vitro), changing above all the dissociation constant after chronic administration, suggests predominantly nonspecific type of binding to the receptors. It is possible that their anxiolytic activity is associated with indirect interactions with one of the components of the GABA-benzodiazepine receptor complex, similar to the atypical tranquillizers.

Amidines↗

PubMed1988

Effect of an original piperazine derivative of tetraline on the adrenergically mediated metabolic responses in cats and rats.

One piperazine derivative of tetraline (with code P11), possessing hypotensive and anti-hypertensive activity, is studied. Its alpha- and beta-adrenoceptor blocking properties are characterized by using indicators of adrenergically mediated metabolic responses in cats and rats. The parameters studied are: glucose and lactate in the blood, free fatty acids in the plasma and the activity of phosphorylase "a" in rat myocardium. The alpha- and beta-adrenergic properties of P11 are characterized by using adrenergic and dopaminergic agonists and antagonists (adrenaline, isoproterenol, phenylephrine, propranolol, phentolamine, apomorphine and pimozide) in the different experimental setups. Compound P11 studied inhibits the effect of phenylephrine on the glucose level in the blood of rats in a definite dose interval (1-4 mg/kg) which suggests that it possesses alpha-adrenoblocking properties. P11 decreases slightly the effects of isoproterenol or does not change these effects on the levels of glucose, lactate and free fatty acids in cats. There are no changes in the effect of adrenaline on the glucose content in rat blood and the isoproterenol-activated phosphorylase in rat myocardium is not inhibited. This gives grounds to assume that P11 possesses slight beta-adrenoblocking properties. From the analysis of the proper hyperglycaemizing action of P11 in rats in the 1-8 mg/kg dose range it may be assumed that dopamine-agonistic mechanisms are involved.

Adrenergic alpha-Antagonists↗

PubMed1986

Possible 5-hydroxytryptamine1 (5-HT1) receptor involvement in the stimulus properties of 1-(m-trifluoromethylphenyl)piperazine (TFMPP).

Male rats (N = 24) were trained to discriminate 1-(m-trifluoromethylphenyl)piperazine (TFMPP) (0.8 mg/kg) from saline in a two-lever, drug discrimination situation. 5-Hydroxytryptamine (5-HT) agonists such as fenfluramine (0.8-1.6 mg/kg), m-chlorophenylpiperazine (0.1-1.6 mg/kg) and RU 24969 (0.1-1.6 mg/kg) mimicked TFMPP; 8-hydroxy-2-(di-n-propylamino)tetralin (0.02-0.32 mg/kg) and quipazine (0.2-3.2 mg/kg) elicited saline lever responding; d-lysergic acid diethylamide (0.1-0.16 mg/kg) produced intermediate results. The 5-HT antagonists BC 105 (1.6-12.8 mg/kg), bromolysergic diethylamide (0.8-1.28 mg/kg), ketanserin (0.8-6.4 mg/kg), Ly 53857 (0.2-1.6 mg/kg) and pirenperone (0.08-0.64 mg/kg) failed to attenuate the TFMPP cue; metergoline (0.4-6.4 mg/kg) and spiperone (0.08-1.28 mg/kg) decreased drug lever responding by as much as 60%. These data suggest that 5-HT agonists are not identical and that drug discrimination procedures can differentiate among them. Given that there is strong evidence to support the existence of heterogeneous 5-HT receptors, the present results also suggest that TFMPP acts through mechanism(s) similar to those of the novel 5-HT1 agonists m-chlorophenylpiperazine and RU 24969; these actions can be differentiated from those underlying d-lysergic acid diethylamide, quipazine and 2,5-dimethoxy-4-methylamphetamine, which are attenuated by putative 5-HT2 antagonists. Thus, the authors propose a role for 5-HT1 receptors in mediating the stimulus effects of TFMPP, although further research is necessary to identify functional antagonists of such systems.

2-Methyl-4-chlorophenoxyacetic Acid↗

PubMed1978

Metabolic effects of some antibilharzial drugs. Comparative study on the effect of tartar-emetic and piperazine hexahydrate on the activity of some oxidoreductase enzymes of the rat livers.

IN THIS INVESTIGATION, the effects of the examined antibilharzial agents are as follows: Bilharcid and tartar-emetic similarly affected succinate oxidation. 50% inhibition could be obtained at a concentration of 10(-3) of both drugs. Malate oxidation was differently affected by the drugs. Bilharcid and tartar-emetic at a concentration of 10(-3) M induced 50% and 70% inhibition respectively, while tartar-emetic stimulated malate oxidation if added in a concentration of 10(-5) M. Pyruvate oxidation was affected in the same manner and to the same extent as malate oxidation. Citrate oxidation was slightly inhibited by Bilharcid and tartar-emetic. 10% and 30% inhibition could be obtained if the concentration was 10(-3) M of both drugs respectively. Bilharcid had a biphasic effect on citrate oxidation. Stimulation could be observed at low concentrations (up to 10(-8) M and inhibition at higher ones (up to 10(-3) M. Piperazine hexahydrate was nearly without effect on the rate of oxidation of the four mentioned substrates.

Animals↗

PubMed1986

Suppression of myocardial protein degradation by the protease inhibitor bis[ethyl(2R,3R)-3-[(S)-methyl-1-[4-(2,3,4-tri-methoxy-phenyl-methyl) piperazine-1-ylcarbonyl]butyl-carbonyl]oxiran-2-carboxylat e]sulfate under hypoxia.

The synthetic protease inhibitor bis[ethyl(2R,3R)-3-[(S)-methyl-1-[4-(2,3,4-tri-methoxyphenyl-methyl) piperazine-1-ylcarbonyl]butyl-carbonyl]oxiran-2-carboxylate] sulfate (NCO-700) suppressed both activities of calcium-activated neutral protease and cathepsin B isolated from cardiac muscle, showing 50% inhibition at 46 and 0.8 mumol/l, respectively. A kinetics study using 14C-labelled NCO-700 suggested its incorporation into cultured myocardial cells, demonstrating the half-maximal saturation time at 17 min. Under both aerobic and hypoxic conditions, the reagent inhibited the peptide release from cultured myocardial cells dose-dependently. The amino acid release from heart slices of adult rabbit was also blocked by the drug under hypoxic and glucose-depleted condition. These data and the myocardial infarction size reducing action of NCO-700 might support the view that NCO-700 sensitive protease(s) - possibly, calcium-activated neutral protease and/or cathepsin B - is (are) working to induce an irreversible proteolysis in the process of myocardial cell degradation.

Aerobiosis↗