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PubMedDate not supplied

[Structural changes in erythrocyte ghosts after irradiation and the initiation of lipid oxidation detectable using 2,6-TNS and fluorescamine].

It was shown on erythrocyte ghosts that the parameters of fluorescence of 2,6-toluidine-naphthalene-sulfonate (2,6-TNS) and fluorescamine undergo similar changes after irradiation. After a dose of 100 Gy the equally effective concentrations of Fe2+ were 1-5 microM and 50-100 microM with regard to changes in the rate of fluorescence of fluorescamine and 2,6-TNS, respectively, and greater than 100 microM with regard to fluorescence anisotropy.

Animals↗
PubMed2001

The DBA/2J strain and prepulse inhibition of startle: a model system to test antipsychotics?

RATIONALE: Prepulse inhibition (PPI) of the startle response in mice is increasingly used as a paradigm of sensory gating with potential predictive and construct validity towards schizophrenia. OBJECTIVES: Establishment of a mouse PPI paradigm in which typical and atypical antipsychotic drugs directly improve a low performance PPI. METHODS: Three strains of mice--C57Bl/6J, 129S6/SvEvTac and DBA/2J--were tested in a startle paradigm with three prepulse intensities, 2, 4 and 8 dB above background. RESULTS: Under these conditions, risperidone (0, 0.25, 0.5 and 1 mg/kg i.p.) and clozapine (0, 1, 3 and 9 mg/kg i.p.) improved PPI in all three strains, with order of effect in DBA/2J > 129S6SvEvTac > C57Bl/6J. The DBA/2J strain showed larger PPI-enhancing effects, without disturbing the basal startle response. Two alpha7 nicotinic receptor agonists, GTS-21 (1-10 mg/kg i.p.) and AR-R17779 (1-10 mg/kg i.p.) were inactive in the PPI procedure in DBA/2J mice. CONCLUSIONS: DBA/2J mice were very sensitive to the antipsychotic-like effects of atypical (clozapine) and typical (risperidone) antipsychotics, and this strain is proposed as a model to directly measure sensory gating properties of drugs. Alpha7 Nicotinergic receptor agonists were ineffective in this PPI paradigm.

Animals↗
PubMed1999

Interaction of anisatin with rat brain gamma-aminobutyric acidA receptors: allosteric modulation by competitive antagonists.

Anisatin, a toxic sesquiterpene isolated from the Japanese star anise (Illicium anisatum L.), competitively inhibited the specific binding of [3H]4'-ethynyl-4-n-propylbicycloorthobenzoate ([3H]EBOB), a non-competitive antagonist of gamma-aminobutyric acid (GABA)A receptors, to rat brain membranes with an IC50 value of 0.43 microM. R 5135, a competitive GABA antagonist, decreased the potency of anisatin in inhibiting [3H]EBOB binding in a negatively cooperative manner. Two other competitive antagonists, SR 95531 (gabazine) and (-)-bicuculline methiodide, had similar effects. On the other hand, R 5135 exerted little influence on the potencies of the other non-competitive antagonists tested: EBOB, picrotoxinin, isopropylbicyclophosphate, and dieldrin. Thus, anisatin was clearly different from the other non-competitive antagonists in responding to the action of competitive antagonists on (GABA)A receptors. These findings suggest that the binding region of anisatin might overlap with that of the other non-competitive antagonists, but that anisatin must interact with other specific region(s).

Affinity Labels↗
PubMed2003

Attentional effects of nicotinic agonists in rats.

Nicotine can increase stimulus detection, response rate and speed in the five-choice serial reaction time task, a rodent test of attention. In the present experiments, four other nicotinic agonists with different pharmacological profiles were compared in the same procedure. The response profile of epibatidine resembled that previously obtained with nicotine in that response accuracy was enhanced and omission errors and correct response latency decreased. ABT-418 transiently increased accuracy in the first 10 min of test sessions and reduced response latency. Isoarecolone caused a dose-related increase in accuracy, but had no effect on omissions or response latency. This absence of effects on response rate- or speed-related measures may be related to its previously reported reduced ability to release dopamine as compared with nicotine. The alpha7-agonist AR-R17779 was without effect on any measure, indicating that this receptor subtype may not mediate nicotinic effects on attention. Affinity constants of compounds, determined in competition binding assays targeting the alpha4beta2, alpha7, alpha3beta4 and alpha3beta2* nAChR subtypes, could not explain the differential behavioural effects observed. Differences in their functional efficacy at nAChR subtypes may instead be responsible. The finding that attentional performance and response rate and speed can be selectively modulated by nicotinic agonists is encouraging for the development of drugs with therapeutic properties similar to those of nicotine but with reduced unwanted effects.

Animals↗
PubMed2001

Semi-synthesis of 2-deoxo- and 3-epi-paraherquamide A.

2-Deoxo- and 3-epi-paraherquamide A were synthesized from paraherquamide A. 2-Deoxoparaherquamide A has good activity against HC and TC in our jird model comparable to the parent compound, while 3-epi-paraherquamide A showed no activity.

Animals↗
PubMed1994

Study of structure/activity relationships by multivariate statistical analysis in a series of triazaspirodecanediones with CNS activities.

The CNS activities of thirteen triazaspirodecanediones have been compared by multivariate statistical analysis. The response parameters used in this study were spontaneous motor activity, potentiation of pentobarbital effect, anticonvulsant and anxiolytic activities. Pharmacological data were analyzed using two methods: (1) a factorial correspondence analysis; (2) an automatic analysis based first on a hierarchical clustering represented by a dendrogram and second on the minimum spanning tree method. The obtained results allow to imagine the synthesis of more specific compounds.

Animals↗
PubMedDate not supplied

Spiroimidazolidinone library derivatives on SynPhase lanterns.

Optimization and solid-phase synthesis of new spiroimidazolidinone derivatives as highly functionalized templates is reported. The synthesis of 1,4,8-triazaspiro[4.5]decan-2-one derivatives was performed on SynPhase lanterns from dipeptides anchored on the solid support and N-protected piperidone. A library of 180 discrete compounds was prepared.

Chromatography, High Pressure Liquid↗
PubMed1989

Inhibition of converting enzyme in the cerebrospinal fluid of rats after oral treatment with converting enzyme inhibitors.

Inhibition of brain converting enzyme (CE) has been implicated in the antihypertensive action of some CE inhibitors. However, it is still a matter of debate whether these drugs gain access to the central nervous system upon systemic administration. In this study in rats we investigated the ability of p.o. applied CE inhibitors to penetrate from blood into cerebrospinal fluid (CSF) by analyzing the inhibition of CE activity in the CSF after acute bolus and after 1 week overnight treatment with enalapril, ramipril and Hoe 288. Penetration into the CSF closely paralleled the lipid solubility of the drugs. The most lipophilic drug, Hoe 288 (10 mg/kg), inhibited CE activity in the CSF after acute (66%) and after chronic (30%) p.o. treatment. Ramipril (10 mg/kg), being less lipophilic than Hoe 288, was only effective after acute bolus administration (59% inhibition), whereas the most hydrophilic drug, enalapril (30 mg/kg), did not reduce CE activity in the CSF after either regimen. The CE inhibition in the CSF after acute p.o. treatment with ramipril and Hoe 288 was dose-dependent with threshold doses of 3 to 10 mg/kg (ramipril) and less than 1 mg/kg (Hoe 288). The presence of ramipril and Hoe 288 in the CSF was also demonstrated by the inhibitory effect of heat-inactivated CSF from CE inhibitor-treated rats on purified CE from rabbit lung. A comparison of the in vitro activities of the three prodrugs and their parent diacids against CE in plasma and in CSF and against purified CE revealed hydrolysis of the prodrugs to their parent diacids in plasma and CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2001

New constituents of the leaves of Alpinia flabellata.

Two new compounds were isolated from the leaves of Alpinia flabellata. The structures of these compounds were determined by a combination of NMR techniques and HREIMS as 4-hydroxy-2-(2,4,5-trimethoxyphenyl)-2E-butenal (1) and rel-labd-12-en-15(16)-olid-7-one-8R-spiro-1'-[2S-(2,4,5-trimethoxyphenyl)-3-cyclohexene] (2).

Aldehydes↗
PubMed2003

Carbohydrate-derived spiroketals: stereoselective synthesis of di-D-fructose dianhydrides via intramolecular aglycon delivery.

[reaction: see text] A one-pot synthesis of C(2)-symmetric di-d-fructose dianhydrides having the 1,6,9,13-tetraoxadispiro [4.2.4.2]tetradecane skeleton has been accomplished via intramolecular aglycon delivery from (6 --> 6) xylylene-tethered fructofuranose precursors. The stereochemical outcome of the glycosylation-spiroketalization process is governed by the geometrical constraints imposed by the rigid tetracyclic structure of the final compound.

Cyclization↗
PubMed1990

[Studies on antitumor drugs: the synthesis of N',N"-dispirotripiperaziniums].

In order to search for new antitumor drugs, sixteen N',N"-dispirotripiperazine derivatives were synthesized from N',N"-dispirotripiperazinium dichloride dihydrochloride by substitution, acylation and Mannich reaction. Six compounds were selected for preliminary pharmacological test. The result showed that five compounds possess inhibitory action against carcinoma S37 in rats. The inhibitory activity of compounds VI and X was 55.0% and 41.9% respectively.

Animals↗
PubMed1999

AR-R17779, and alpha7 nicotinic agonist, improves learning and memory in rats.

Nicotinic acetylcholine systems have been found to be important for learning and memory function. The prototypic nicotinic agonist nicotine has been shown in a variety of studies to improve aspects of cognitive function. The specific involvement of nicotinic receptor subtypes is now being investigated. The involvement of alpha7 nicotinic receptors was assessed in this project using a novel alpha7 nicotinic agonist, AR-R 17779. Repeated doses (subcutaneous injection 20 min before testing) of the racemic mixture AR-R 13489 and its active isomer AR-R 17779 were assessed in adult female Sprague-Dawley rats using the eight-arm radial maze. AR-R 13489 (2 mg/kg) caused a significant improvement of long-term win-shift acquisition after 3 weeks of training (n = 10 per group). The same dose of AR-R 17779 also caused a significant improvement in repeated acquisition within each daily session in the radial-arm maze. In another study, the active isomer AR-R 17779 significantly improved radial-arm maze working memory function in rats with lesions to the septohippocampal projection. Fimbria-fornix lesions significantly impaired working memory performance and AR-R 17779 significantly reversed that impairment. These studies showed that alpha7 nicotinic agonist treatment improved learning in two radial-arm maze tasks and reversed working memory impairment caused by fimbria-fornix sections, providing evidence for alpha7 involvement in learning and memory, and the potential therapeutic use of AR-R 17779.

Animals↗