Método extendido de Hildebrand en la predicción de la solubilidad del ketoprofeno en mezclas cosolventes etanol + agua

Extended Hildebrand Solubility Approach (EHSA) developed by Martin et al. was applied to evaluate the solubility of ketoprofen (KTP) in ethanol + water cosolvent mixtures at 298.15 K. Calculated values of molar volume and solubility parameter for KTP were used. A good predictive capacity of EHSA was found by using a regular polynomial model in order five to correlate the W interaction parameter and the solubility parameters of cosolvent mixtures (δmix). Nevertheless, the deviations obtained in the estimated solubilities with respect to the experimental solubilities were on the same order like those obtained directly by means of an empiric regression of the logarithmic experimental solubilities as a function of δmix values.

Uso de redes neurais recorrentes na determinação das constantes de acidez para a 7-epiclusianona em misturas etanol-água

This work propose a recursive neural network to solve inverse equilibrium problem. The acidity constants of 7-epiclusianone in ethanol-water binary mixtures were determined from multiwavelength spectrophotmetric data. A linear relationship between acidity constants and the %w/v of ethanol in the solvent mixture was observed. The proposed method efficiency is compared with the Simplex method, commonly used in nonlinear optimization techniques. The neural network method is simple, numerically stable and has a broad range of applicability.

Autoagregação da 5,10,15,20-tetrakis(4-metoxifenil)porfirina (tmpp): estudos espectroscópicos e análises multivariadas

In this work, the spectroscopic properties of 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMPP) in solvents of different polarities and water/ethanol mixtures were studied by electronic absorption spectroscopy and resonance light scattering associated with statistical analysis. The molar absorption coefficient and emission maximum of TMPP were dependent on solvent polarity. In the water/ethanol mixture, TMPP remained monomeric up to 25% of water, when it reaches its critical aggregation percentage. Oblique head-to-tail aggregate was found at intermediate water content (35 - 55%), while formation of a J-type aggregate was observed at higher water content (> 60%).

Inotropic effects of extracts of Psidium guajava L. (guava) leaves on the guinea pig atrium

Many pharmacological effects have been ascribed to extracts of Psidium guajava L. (guava) leaves. However, in spite of its widespread use in Brazilian folk medicine and a reasonable number of scientific reports about it, we could not find any study dealing with its action on the mammalian myocardium. In the present study, by measuring isometric force, we observed that the crude extract of P. guajava (water-alcohol extract obtained by macerating dry leaves) depresses the guinea pig atrial contractility in a concentration-dependent fashion (N = 8 hearts, 15 trials). The compound with cardiac activity was concentrated by extraction in a Soxhlet apparatus using 17 M glacial acetic acid after removing the less polar fractions (hexane, chloroform, acetone, ethanol and methanol), suggesting that this compound is a highly polar substance. In the isolated guinea pig left atrium the acetic acid fraction (10-800 mg/l) of P. guajava 1) reversibly decreased myocardial force in a concentration-dependent fashion (EC50 = 0.07g/l, N = 5 hearts, 9 trials, P<0.05), 2) increased the atrial relaxation time measured at 20% of the force amplitude up to 35% (91 ± 15 to 123 ± 30 ms, N = 3 hearts, 6 trials, P<0.05), 3) abolished the positive staircase effect (Bowditch phenomenon) in a concentration-dependent fashion suggesting a decrease of the cellular inward calcium current (N = 4 hearts, 8 trials, P<0.05), and 4) its inotropic effect was abolished by cholinergic receptor blockade with 1.5 mM atropine sulfate, indicating a cholinergic involvement in the mechanism of action of the extract (N = 7 hearts, 15 trials, P<0.05). The acetic acid extract was 20 times more potent than crude extract (EC50 = 1.4 g/l). The results showed that extracts from P. guajava leaves depress myocardial inotropism.

Effect of Erythrina velutina and Erythrina mulungu in rats submitted to animal models of anxiety and depression

Erythrina velutina (EV) and Erythrina mulungu (EM), popularly used in Brazil as tranquilizing agents, were studied. The effects of acute and chronic oral treatment with a water:alcohol extract of EV (7:3, plant grounded stem bark; acute = 100, 200, 400 mg/kg; chronic = 50, 100, 200 mg/kg) were evaluated in rats (N = 11-12) submitted to the elevated T-maze (for avoidance and escape measurements) model of anxiety. This model was selected for its presumed capacity to elicit specific subtypes of anxiety disorders recognized in clinical practice: avoidance has been related to generalized anxiety and escape to panic. Additionally, animals were treated with the same doses of EV and EM (water:alcohol 7:3, inflorescence extract) and submitted to the forced swim test for the evaluation of antidepressant activity (N = 7-10). Both treatment regimens with EV impaired elevated T-maze avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (avoidance 1, mean ± SEM, acute study: 131.1 ± 45.5 (control), 9.0 ± 3.3 (diazepam), 12.7 ± 2.9 (200 mg/kg), 28.8 ± 15.3 (400 mg/kg); chronic study: 131.7 ± 46.9 (control), 35.8 ± 29.7 (diazepam), 24.4 ± 10.4 (50 mg/kg), 29.7 ± 11.5 (200 mg/kg)). Neither EV nor EM altered measurements performed in the forced swim test, in contrast to the reference drug imipramine that significantly decreased immobility time after chronic treatment. These results were not due to motor alterations since no significant effects were detected in an open field. These observations suggest that EV exerts anxiolytic-like effects on a specific subset of defensive behaviors which have been associated with generalized anxiety disorder.

The effects of additives and chemical modification on the solution properties of thermo-sensitive polymers

Cette thèse concerne l’étude de phase de séparation de deux polymères thermosensibles connus-poly(N-isopropylacylamide) (PNIPAM) et poly(2-isopropyl-2-oxazoline) (PIPOZ). Parmi des études variées sur ces deux polymères, il y a encore deux parties de leurs propriétés thermiques inexplicites à être étudiées. Une partie concerne l’effet de consolvant de PNIPAM dans l’eau et un autre solvant hydromiscible. L’autre est l’effet de propriétés de groupes terminaux de chaînes sur la séparation de phase de PIPOZ. Pour ce faire, nous avons d’abord étudié l’effet de l’architecture de chaînes sur l’effet de cosolvant de PNIPAMs dans le mélange de méthanol/eau en utilisant un PNIPAM en étoile avec 4 branches et un PNIPAM cyclique comme modèles. Avec PNIPAM en étoile, l’adhérence de branches PNIPAM de à un cœur hydrophobique provoque une réduction de Tc (la température du point de turbidité) et une enthalpie plus faible de la transition de phase. En revanche, la Tc de PNIPAM en étoile dépend de la masse molaire de polymère. La coopérativité de déhydratation diminue pour PNIPAM en étoile et PNIPAM cyclique à cause de la limite topologique. Une étude sur l’influence de concentration en polymère sur l’effet de cosolvant de PNIPAM dans le mélange méthanol/eau a montré qu’une séparation de phase liquide-liquide macroscopique (MLLPS) a lieu pour une solution de PNIPAM dans le mélange méthanol/eau avec la fraction molaire de méthanol entre 0.127 et 0.421 et la concentration en PNIPAM est constante à 10 g.L-1. Après deux jours d’équilibration à température ambiante, la suspension turbide de PNIPAM dans le mélange méthanol/eau se sépare en deux phases dont une phase possède beaucoup plus de PNIPAM que l’autre. Un diagramme de phase qui montre la MLLPS pour le mélange PNIPAM/eau/méthanol a été établi à base de données expérimentales. La taille et la morphologie de gouttelettes dans la phase riche en polymère condensée dépendent de la fraction molaire de méthanol. Parce que la présence de méthanol influence la tension de surface des gouttelettes liquides, un équilibre lent de la séparation de phase pour PNIPAM/eau/méthanol système a été accéléré et une séparation de phase liquide-liquide macroscopique apparait. Afin d’étudier l’effet de groupes terminaux sur les propriétés de solution de PIPOZ, deux PIPOZs téléchéliques avec groupe perfluorodécanyle (FPIPOZ) ou groupe octadécyle (C18PIPOZ) comme extrémités de chaîne ont été synthétisés. Les valeurs de Tc des polymères téléchéliques ont beaucoup diminué par rapport à celle de PIPOZ. Des micelles stables se forment dans des solutions aqueuses de polymères téléchéliques. La micellization et la séparation de phase de ces polymères dans l’eau ont été étudiées. La séparation de phase de PIPOZs téléchéliques suit le mécanisme de MLLPS. Des différences en tailles de gouttelettes formées à l’intérieur de solutions de deux polymères ont été observées. Pour étudier profondément les différences dans le comportement d’association entre deux polymères téléchéliques, les intensités des signaux de polymères correspondants et les temps de relaxation T1, T2 ont été mesurés. Des valeurs de T2 de protons correspondants aux IPOZs sont plus hautes.

Design and study of self-assembled functional organic and hybrid systems for biological applications

The focus of self-assembly as a strategy for the synthesis has been confined largely to molecules, because of the importance of manipulating the structure of matter at the molecular scale. We have investigated the influence of temperature and pH, in addition to the concentration of the capping agent used for the formation of the nano-bio conjugates. For example, the formation of the narrower size distribution of the nanoparticles was observed with the increase in the concentration of the protein, which supports the fact that γ-globulin acts both as a controller of nucleation as well as stabiliser. As analyzed through various photophysical, biophysical and microscopic techniques such as TEM, AFM, C-AFM, SEM, DLS, OPM, CD and FTIR, we observed that the initial photoactivation of γ-globulin at pH 12 for 3 h resulted in small protein fibres of ca. Further irradiation for 24 h, led to the formation of selfassembled long fibres of the protein of ca. 5-6 nm and observation of surface plasmon resonance band at around 520 nm with the concomitant quenching of luminescence intensity at 680 nm. The observation of light triggered self-assembly of the protein and its effect on controlling the fate of the anchored nanoparticles can be compared with the naturally occurring process such as photomorphogenesis.Furthermore,our approach offers a way to understand the role played by the self-assembly of the protein in ordering and knock out of the metal nanoparticles and also in the design of nano-biohybrid materials for medicinal and optoelectronic applications. Investigation of the potential applications of NIR absorbing and water soluble squaraine dyes 1-3 for protein labeling and anti-amyloid agents forms the subject matter of the third chapter of the thesis. The study of their interactions with various proteins revealed that 1-3 showed unique interactions towards serum albumins as well as lysozyme. 69%, 71% and 49% in the absorption spectra as well as significant quenching in the fluorescence intensity of the dyes 1-3, respectively. Half-reciprocal analysis of the absorption data and isothermal titration calorimetric (ITC) analysis of the titration experiments gave a 1:1 stoichiometry for the complexes formed between the lysozyme and squaraine dyes with association constants (Kass) in the range 104-105 M-1. We have determined the changes in the free energy (ΔG) for the complex formation and the values are found to be -30.78, -32.31 and -28.58 kJmol-1, respectively for the dyes 1, 2 and 3. Furthermore, we have observed a strong induced CD (ICD) signal corresponding to the squaraine chromophore in the case of the halogenated squaraine dyes 2 and 3 at 636 and 637 nm confirming the complex formation in these cases. To understand the nature of interaction of the squaraine dyes 1-3 with lysozyme, we have investigated the interaction of dyes 1-3 with different amino acids. These results indicated that the dyes 1-3 showed significant interactions with cysteine and glutamic acid which are present in the side chains of lysozyme. In addition the temperature dependent studies have revealed that the interaction of the dye and the lysozyme are irreversible. Furthermore, we have investigated the interactions of these NIR dyes 1-3 with β- amyloid fibres derived from lysozyme to evaluate their potential as inhibitors of this biologically important protein aggregation. These β-amyloid fibrils were insoluble protein aggregates that have been associated with a range of neurodegenerative diseases, including Huntington, Alzheimer’s, Parkinson’s, and Creutzfeldt-Jakob diseases. We have synthesized amyloid fibres from lysozyme through its incubation in acidic solution below pH 4 and by allowing to form amyloid fibres at elevated temperature. To quantify the binding affinities of the squaraine dyes 1-3 with β-amyloids, we have carried out the isothermal titration calorimetric (ITC) measurements. The association constants were determined and are found to be 1.2 × 105, 3.6× 105 and 3.2 × 105 M-1 for the dyes, 1-3, respectively. To gain more insights into the amyloid inhibiting nature of the squaraine dyes under investigations, we have carried out thioflavin assay, CD, isothermal titration calorimetry and microscopic analysis. The addition of the dyes 1-3 (5μM) led to the complete quenching in the apparent thioflavin fluorescence, thereby indicating the destabilization of β-amyloid fibres in the presence of the squaraine dyes. Further, the inhibition of the amyloid fibres by the squaraine dyes 1-3, has been evidenced though the DLS, TEM AFM and SAED, wherein we observed the complete destabilization of the amyloid fibre and transformation of the fibre into spherical particles of ca. These results demonstrate the fact that the squaraine dyes 1-3 can act as protein labeling agents as well as the inhibitors of the protein amyloidogenesis. The last chapter of the thesis describes the synthesis and investigation of selfassembly as well as bio-imaging aspects of a few novel tetraphenylethene conjugates 4-6.Expectedly, these conjugates showed significant solvatochromism and exhibited a hypsochromic shift (negative solvatochromism) as the solvent polarity increased, and these observations were justified though theoretical studies employing the B3LYP/6-31g method. We have investigated the self-assembly properties of these D-A conjugates though variation in the percentage of water in acetonitrile solution due to the formation of nanoaggregates. Further the contour map of the observed fluorescence intensity as a function of the fluorescence excitation and emission wavelength confirmed the formation of J-type aggregates in these cases. To have a better understanding of the type of self-assemblies formed from the TPE conjugates 4-6, we have carried out the morphological analysis through various microscopic techniques such as DLS, SEM and TEM. 70%, we observed rod shape architectures having ~ 780 nm in diameter and ~ 12 μM in length as evidenced through TEM and SEM analysis. We have made similar observations with the dodecyl conjugate 5 at ca. 70% and 50% water/acetonitrile mixtures, the aggregates formed from 4 and 5 were found to be highly crystalline and such structures were transformed to amorphous nature as the water fraction was increased to 99%. To evaluate the potential of the conjugate as bio-imaging agents, we have carried out their in vitro cytotoxicity and cellular uptake studies though MTT assay, flow cytometric and confocal laser scanning microscopic techniques. Thus nanoparticle of these conjugates which exhibited efficient emission, large stoke shift, good stability, biocompatibility and excellent cellular imaging properties can have potential applications for tracking cells as well as in cell-based therapies. In summary we have synthesized novel functional organic chromophores and have studied systematic investigation of self-assembly of these synthetic and biological building blocks under a variety of conditions. The investigation of interaction of water soluble NIR squaraine dyes with lysozyme indicates that these dyes can act as the protein labeling agents and the efficiency of inhibition of β-amyloid indicate, thereby their potential as anti-amyloid agents.

Influence of the solvent on the self-assembly of a modified amyloid beta peptide fragment. I. Morphological investigation

The solvent-induced transition between self-assembled structures formed by the peptide AAKLVFF is studied via electron microscopy, light scattering, and spectroscopic techniques. The peptide is based on a core fragment of the amyloid beta-peptide, KLVFF, extended by two alanine residues. AAKLVFF exhibits distinct structures of twisted fibrils in water or nanotubes in methanol. For intermediate water/methanol compositions, these structures are disrupted and replaced by wide filamentous tapes that appear to be lateral aggregates of thin protofilaments. The orientation of the beta-strands in the twisted tapes or nanotubes can be deduced from X-ray diffraction on aligned stalks, as well as FT-IR experiments in transmission compared to attenuated total reflection. Strands are aligned perpendicular to the axis of the twisted fibrils or the nanotubes. The results are interpreted in light of recent results on the effect of competitive hydrogen bonding upon self-assembly in soft materials in water/methanol mixtures.

Effect of ethanol on the micellization and gelation of Pluronic P123

In certain applications copolymer P123 (E21P67E21) is dissolved in water-ethanol mixtures, initially to form micellar solutions and eventually to gel. For P123 in 10, 20, and 30 wt % aqueous ethanol we used dynamic light scattering from dilute solutions to confirm micellization, oscillatory rheometry, and visual observation of mobility (tube inversion) to determine gel formation in concentrated solutions and small-angle X-ray scattering (SAXS) to determine gel structure. Except for solutions in 30 wt % aqueous ethanol, a clear-turbid transition was encountered on heating dilute and concentrated micellar solutions alike, and as for solutions in water alone (Chaibundit et al. Langmuir 2007, 23, 9229) this could be ascribed to formation of wormlike micelles. Dense clouding, typical of phase separation, was observed at higher temperatures. Regions of isotropic and birefringent gel were defined for concentrated solutions and shown (by SAXS) to have Cubic (fcc and hcp) and hexagonal structures, consistent with packed spherical and elongated micelles, respectively. The cubic gels (0, 10, and 20 wt % ethanol) were clear, while the hex gels were either turbid (0 and 10 wt % ethanol), turbid enclosing a clear region (20 wt % ethanol), or entirely clear (30 wt % ethanol). The SAXS profile was unchanged between turbid and clear regions of the 20 wt % ethanol gel. Temperature scans of dynamic moduli showed (as expected) a clear distinction between high-modulus cubic gels (G'(max) approximate to 20-30 kPa) and lower modulus hex gels (G'(max) < 10 kPa).

Aspectos dinâmicos da água versus álcool e acetona por técnicas de congelamento

Water still represents, on its critical properties and phase transitions, a problem of current scientific interest, as a consequence of the countless open questions and of the inadequacy of the existent theoretical models, mainly related to the different solid and liquid phases that this substance possesses. For example, there are 13 known crystalline forms of water, and also amorphous phases. One of them, the amorphous ice of very high density (VHDA), was just recently observed. Other example is the anomalous behavior in the macroscopic density, which presents a maximum at the temperature of 277 K. In order to experimentally investigate the behavior of one of the liquid-solid phase transitions, the anomaly in its density and also the metastability, we used three different cooling techniques and, as comparison systems, we made use of the solvents: acetone and ethyl alcohol. The first studied cooling system employ a Peltier plate, a device recently developed, which makes use of small cubes made up of semiconductors to change heat among two surfaces; the second system is a commercial refrigerator, similar to the residential ones. Finally, the liquid nitrogen technique, which is used to refrigerate the samples in a container, in two ways: a very fast and other one, almost static. In those three systems, three Beckers of aluminum were used (with a volume of 80 ml, each), containing water, alcohol and acetone. They were closed and maintained at atmospheric pressure. Inside of each Becker were installed three thermocouples, disposed along the vertical axis of the Beckers, one close to the inferior surface, other to the medium level and the last one close the superior surface. A system of data acquisition was built via virtual instrumentation using as a central equipment a Data-Acquisition board. The temperature data were collected by the three thermocouples in the three Beckers, simultaneously, in function of freezing time. We will present the behavior of temperature versus freezing time for the three substances. The results show the characterization of the transitions of the liquid

Thermal characterization of an ultrasonic density-measurement cell

An ultrasonic density-measurement cell is experimentally characterized as a function of temperature. The measurement of propagation velocity and density of several liquids is performed in the 15 degrees C-40 degrees C temperature range. Results are compared to the tabulated values in the case of distilled water, showing an accuracy of 0.07% for the propagation velocity. The cell was tested with distilled water, alcohol, and homogenized milk, and density values are compared to those obtained with a pycnometer, showing 0.2% accuracy in density measurement for stabilized temperature and 0.4% accuracy under thermal gradient conditions.

A kinetic study of the effect of ultrasound power on the sonohydrolysis of tetraethyl orthosilicate

A kinetic study of the ultrasound-stimulated and acid-catalyzed sonohydrolysis of tetraethyl orthosilicate (TEOS) in solventless TEOS-water heterogeneous mixtures was carried out by means of a calorimetric method as a function of the ultrasound power. The hydrolysis reaction starts in acidulated heterogeneous water-TEOS mixtures after an induction period under ultrasonic stimulation. The ultrasound power seems to play a role on the dynamical coupling of the system originating a continuum upward shifting of the base line during the induction period of sonication. The rate in which the base line is upward shifted diminishes with the power. The best coupling between the ultrasound and the reactant heterogeneous mixtures for this experimental setup was found to occur at 50 W, for which the gelation time was found to be a minimum. The kinetics of the heterogeneous TEOS sonohydrolysis was studied on the basis of a dissolution and reaction modeling. The heterogeneous reaction pathway as deduced from the kinetic study was drawn in a ternary diagram as a function of the ultrasound power. (C) 2006 Elsevier B.V. All rights reserved.

Prospecção de moléculas químicas com propriedades alelopáticas em Acacia mangium (Willd.)

Muito se tem estudado sobre o potencial que algumas plantas têm de inibir o desenvolvimento de outras plantas. Em busca de alternativas para reduzir a dependência de herbicidas sintéticos, diminuindo os danos ambientais e prejuízos à saúde humana e procurando alternativas à resistência aos herbicidas do mercado, os compostos naturais oferecem excelentes perspectivas. Este trabalho isola, identifica as estruturas e caracteriza a atividade alelopática de duas substâncias químicas produzidas pela espécie Acacia mangium. Para isso, procede-se com solução hidroalcoólica (7:3) extração exaustiva das folhas secas caídas, folhas verdes, raízes e sementes dessa espécie, passando-se pela recuperação do etanol (evaporador rotativo) e liofilização dos extratos para a desidratação e obtenção do extrato bruto hidroalcoólico (EBHA). Para identificar qual parte da planta possui maior potencial alelopático, é preparado um bioensaio com a utilização de solução hidroalcoólica (7:1) de cada EBHA em concentração de 1%. É determinado o potencial inibitório sobre a germinação, desenvolvimento do hipocótilo e desenvolvimento da radícula das sementes das plantas daninhas malícia (Mimosa pudica), mata-pasto (Senna alata) e puerária (Pueraria phaseoloides). 10 g do EBHA das folhas caídas são submetidas à CCVU para separação das substâncias, a partir do qual são obtidas quatro reuniões de substâncias semelhantes. Três delas são refracionadas em colunas menores (R1’, R2- R3’, R4’) e da coluna R1’ são isoladas as substâncias Lupenona e Lupeol. Nos bioensaios com os extratos, o das folhas secas apresenta as inibições mais acentuadas, notadamente sobre a germinação (99%). Nesta característica, mata-pasto é a espécie de menor sensibilidade, com inibições abaixo de 12%. São realizados bioensaios com as substâncias isoladas e em par (solubilizadas em clorofórmio), na concentração de 140 ppm, sobre as sementes de Mimosa pudica e Senna obtusifolia. Para a germinação das sementes, as substâncias em todos os tratamentos não evidenciam qualquer efeito. Para o desenvolvimento da radícula, ambas as substâncias, isoladamente, promovem inibições em torno de 40% sobre duas espécies de plantas daninhas, enquanto que em par, observa-se que há antagonismo entre as substâncias, já que os resultados são inferiores, ficando ao redor de 30%. Com relação ao crescimento do hipocótilo a inibição em todos os tratamentos fica em torno de 15% e não há diferença significativa entre os resultados. É testado também o efeito do pH (3,0 e 9,0) na atividade alelopática das substâncias, isoladas e em par, sobre a germinação das sementes de malícia e observa-se que há interação para os fatores pH e germinação, havendo maior atividade inibitória da lupenona em condições ácidas e do lupeol em condições alcalinas. Não há efeito aditivo ou negativo quando da associação das substâncias. É realizada também análise por HPLC nos extratos brutos hidroalcoólicos de três partes da planta Acacia mangium para a detecção dos flavonóides catequina e epicatequina (substâncias com comprovado efeito alelopático), sendo que a epicatequina é a substância com absorção para os espetros selecionados, mostrando que esta substância pode ter contribuído para os resultados expressivos observados nos primeiros bioensaios com os extratos brutos das partes das plantas.

Micropartículas de metotrexato e ácido poli lático-co-glicólico obtidas por “spray-drying”

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Erysothrine, an alkaloid extracted from flowers of Erythrina mulungu Mart. ex Benth: Evaluating its anticonvulsant and anxiolytic potential

In this study, we isolated the alkaloid erysothrine from the hydroalcoholic extract of flowers from E. mulungu and screened for its anticonvulsant and anxiolytic actions based on neuroethological and neurochemical experiments. Our results showed that the administration of erysothrine inhibited seizures evoked by bicuculline, PTZ, NMDA and most remarkably, kainic acid. Also, erysothrine induced an increase in the number of entries but not in the time spent in the open arms of the EPM. However, we did not notice any alterations in the light-dark choice or in the open-field tests. In preliminary neurochemistry tests, we also showed that erysothrine (0.001-10 mu g/mL) did not alter the GABA or glutamate synaptossomal uptake and binding. Altogether, our results describe an alkaloid with anticonvulsant activity and mild anxiolytic activity that might be considered well tolerated as it does not alter the general behavior of the animals in the used doses. (C) 2012 Elsevier Inc. All rights reserved.