Rapid Study on Mefloquine Hydrochloride Complexation with Hydroxypropyl-ß-Cyclodextrin and Randomly Methylated ß-Cyclodextrin: Phase Diagrams, Nuclear Magnetic Resonance Analysis, and Stability Assessment.

This study investigates the complexation of mefloquine hydrochloride by cyclodextrins to improve its solubility in order to design an oral solution. This approach may enhance the effectiveness of mefloquine, a drug which can be used for malaria prophylaxis and treatment in children. Mefloquine hydrochloride's solubility was assessed in different buffer solutions, and its quantification was achieved through high-performance liquid chromatography. The complexation efficiency with cyclodextrins was evaluated, and nuclear magnetic resonance (NMR) methods were employed to determine the interactions between mefloquine and cyclodextrins. Mefloquine's solubility increased when combined with hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and randomly methylated ß-cyclodextrin (RAMEB), with RAMEB being more effective. The drug's solubility varied across different pH buffers, being higher in acidic buffers. Interestingly, mefloquine's solubility decreased with a citrate buffer, possibly due to precipitation. The NMR studies highlighted non-covalent interactions between RAMEB, HP-ß-CD, and mefloquine, explaining the solubilizing effect via complexation phenomena. Furthermore, the NMR experiments indicated the complexation of mefloquine by all the studied cyclodextrins, forming diastereoisomeric complexes. Cyclodextrin complexation improved mefloquine's solubility, potentially impacting its bioavailability.

Proton tautomerism and stereoisomerism in 5-[(dimethylamino)methylidene]-4-[3/4-(trifluoromethylphenyl)amino]-1,3-thiazol-2(5H)-ones: synthesis, crystal structure and spectroscopic studies.

5-[(Dimethylamino)methylidene]-4-{[3-(trifluoromethyl)phenyl]amino}-1,3-thiazol-2(5H)-one and the [4-(trifluoromethyl)phenyl]amino derivative, both C13H12F3N3OS, with the trifluoromethyl group substituted at the arene ring at the meta and para positions, were synthesized to study the structural changes associated with proton tautomerism of the amidine system. The studied compounds were found to be in the amine tautomeric form in both the solid and the liquid (dimethyl sulfoxide solutions) phase. In both isomers, the [(trifluoromethyl)phenyl]amino residue assumes a synperiplanar conformation with respect to the thiazolone system, while the 5-[(dimethylamino)methylidene] residue adopts the Z configuration. Density functional theory (DFT) calculations correctly predicted that the synperiplanar arrangement is favoured in both isomers. In the crystal, the whole independent molecule of the para compound is disordered over two alternative positions, with occupancy factors of 0.926 (3) and 0.074 (3).

Development of an open-source software for isomer enumeration.

This article documents enu, a freely-downloadable, open-source and stand-alone program written in C++ for the enumeration of the constitutional isomers and stereoisomers of a molecular formula. The program relies on graph theory to enumerate all the constitutional isomers of a given formula on the basis of their canonical adjacency matrix. The stereoisomers of a given constitutional isomer are enumerated as well, on the basis of the automorphism group of this matrix. The isomer list is then reported in the form of canonical SMILES strings within files in XML format. The specification of the molecule family of interest is very flexible and the code is optimized for computational efficiency. The algorithms and implementations underlying enu are described, and simple illustrative applications are presented. The enu code is freely available on GitHub at https://github.com/csms-ethz/CombiFF .

The association of chiral characteristic with drug withdrawal due to safety: A comparative analysis.

AIMS: Chirality of drugs might be associated with safety issues through pharmacokinetic or pharmacodynamic variations, interactions, or direct toxicological responses. We aimed to compare chiral status of the available drugs to that of drugs withdrawn due to adverse drug reactions (ADRs). METHODS: We searched the literature regarding withdrawn drugs due to safety-related issues (n = 391) to compare them with all available small-molecule drugs (n = 1633). We examined their chiral status and assigned as achiral compound, chiral mixture or pure enantiomer. We compared the mean survival (i.e., nonwithdrawal) time and withdrawal rates of drugs by their chirality, with further stratification by the launch year, ATC-1 (Anatomical Therapeutic Chemical) level and ADR. RESULTS: We identified higher withdrawal rate in achiral drugs (hazard ratio 2.1, 95% CI: 1.6-2.7) and chiral mixtures (hazard ratio 2.6, 95% CI: 1.9-3.5) compared to that in pure enantiomers. Pure enantiomers had the longest mean survival time (62.4 ± 0.8 years), followed by achiral drugs (55.4 ± 0.9 years, P < .01) and chiral mixtures (52.4 ± 1.4 years, P < .01). Pure enantiomers had higher survival rates than chiral mixtures if launched before 1941 (P = .02), in 1961-1980 (P < .001) or 1981-2000 (P < .001). Pure enantiomers had lower withdrawal rate (18.2%) vs. chiral mixtures (35.1%, P = .02) in nervous system drugs. Pure enantiomers had lower withdrawal rate than chiral mixtures in hepatotoxic (P < .01) and cardiovascular ADRs (P < .01). CONCLUSION: Our study showed lower likelihood of withdrawal for pure enantiomers compared to that in chiral mixtures and achiral drugs, which was more remarkable for those launched in certain time periods and several ADRs, including hepatotoxicity and cardiovascular toxicity.

Geometric isomers of dichloridoiron(III) complexes of CTMC (5,7,12,14-tetramethyl-1,4,8,11-tetraazacyclotetradecane).

Both trans and cis iron-CTMC complexes, namely, trans-dichlorido[(5SR,7RS,12RS,14SR)-5,7,12,14-tetramethyl-1,4,8,11-tetraazacyclotetradecane]iron(III) tetrachloridoferrate, [Fe(C14H32N4)Cl2][FeCl4] (1a), the analogous chloride methanol monosolvate, [Fe(C14H32N4)Cl2]Cl·CH3OH (1b), and cis-dichlorido[(5SR,7RS,12SR,14RS)-5,7,12,14-tetramethyl-1,4,8,11-tetraazacyclotetradecane]iron(III) chloride, [Fe(C14H32N4)Cl2]Cl (2), were successfully synthesized and structurally characterized using X-ray diffraction. The coordination geometry of the macrocycle is dependent on the stereoisomerism of CTMC. The packing of these complexes appears to be strongly influenced by extensive hydrogen-bonding interactions, which are in turn determined by the nature of the counter-anions (1a versus 1b) and/or the coordination geometry of the macrocycle (1a/1b versus 2). These observations are extended to related ferric cis- and trans-dichloro macrocyclic complexes.

Atropopeptides are a Novel Family of Ribosomally Synthesized and Posttranslationally Modified Peptides with a Complex Molecular Shape.

Biomacromolecules are known to feature complex three-dimensional shapes that are essential for their function. Among natural products, ambiguous molecular shapes are a rare phenomenon. The hexapeptide tryptorubin A can adopt one of two unusual atropisomeric configurations. Initially hypothesized to be a non-ribosomal peptide, we show that tryptorubin A is the first characterized member of a new family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) that we named atropopeptides. The sole modifying enzyme encoded in the gene cluster, a cytochrome P450 monooxygenase, is responsible for the atropospecific formation of one carbon-carbon and two carbon-nitrogen bonds. The characterization of two additional atropopeptide biosynthetic pathways revealed a two-step maturation process. Atropopeptides promote pro-angiogenic cell functions as indicated by an increase in endothelial cell proliferation and undirected migration. Our study expands the biochemical space of RiPP-modifying enzymes and paves the way towards the chemoenzymatic utilization of atropopeptide-modifying P450s.

Design, Synthesis and Biological Evaluation of Neogliptin, a Novel 2-Azabicyclo[2.2.1]heptane-Based Inhibitor of Dipeptidyl Peptidase-4 (DPP-4).

Compounds that contain (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid substituted with bicyclic amino moiety (2-aza-bicyclo[2.2.1]heptane) were designed using molecular modelling methods, synthesised, and found to be potent DPP-4 (dipeptidyl peptidase-4) inhibitors. Compound 12a (IC50 = 16.8 ± 2.2 nM), named neogliptin, is a more potent DPP-4 inhibitor than vildagliptin and sitagliptin. Neogliptin interacts with key DPP-4 residues in the active site and has pharmacophore parameters similar to vildagliptin and sitagliptin. It was found to have a low cardiotoxic effect compared to sitagliptin, and it is superior to vildagliptin in terms of ADME properties. Moreover, compound 12a is stable in aqueous solutions due to its low intramolecular cyclisation potential. These findings suggest that compound 12a has unique properties and can act as a template for further type 2 diabetes mellitus drug development.

A minimal cage of a diamond twin with chirality.

A network of tetrahedral vertices can fill three-dimensional (3D) spaces in a beautiful and isotropic manner, which is found as diamonds with sp3-hybridized carbon atoms. Although a network of trigonal vertices (i.e., another form of carbon atoms with sp2-hybridization) naturally results in a lower-dimensional two-dimensional network of graphenes, an isotropic 3D arrangement of trigonal vertices has been of theoretical and mathematical interest, which has materialized as a proposal of a "diamond twin." We herein report the synthesis and optical resolution of a minimal cage of a chiral diamond-twin network. With triangular phenine units at 14 vertices, triply fused decagonal rings were assembled by forming 15 biaryl edges via coupling. A unique chirality of the network has been disclosed with the minimal cage, which may stimulate explorations of chiral carbonaceous materials.

Base- and Metal-Dependent Self-Assembly of Lathanide-Organic Coordination Polymers or Macrocycles with Tetradentate Acylhydrazone-based Ditopic Ligands.

Herein, we report a comprehensive study on the lanthanide-directed coordination self-assembly with two bis-tetradentate acylhydrazone ligands H4 L1 and H4 L2 . Multifarious outcomes, which are base- and metal-dependent, were revealed by NMR, ESI-TOF-MS and X-ray crystallography. In the absence of base, bent H4 L1 was assembled into dinuclear double-strand helicate Ln2 (H2 L1 )2 by partially-deprotonated assembly with La, Sm or Eu, while trinuclear Ln3 (H2 L1 )3 with Yb or Lu. For linear H4 L2 , infinite 1D zig-zag metal-organic polymeric chain (Ln2 H2 L2 )n was obtained. However, complete deprotonated L1 and L2 assembled into discrete trinuclear Ln3 (L1 /2 )3 and tetranuclear Ln4 (L1 /2 )4 macrocyclic structures under the basic condition. For these, there are multiple possible isomers coexisting in the solution which were enumerated and simulated with molecular mechanic modeling. Visible-light sensitized NIR emissions on the Yb complexes have been observed, endowing them potential application in photofunctional materials.

Combined experimental and quantum mechanical elucidation of the synthetically accessible stereoisomers of Hydroxyestradienone (HED), the starting material for vilaprisan synthesis.

Selective progesterone receptor modulators are promising therapeutic options for the treatment of uterine fibroids. Vilaprisan, a new chemical entity that was discovered at Bayer is currently in clinical development. In this study we provide a combined experimental and quantum chemical approach providing the data that allowed to present hydroxyestradienone as an acceptable starting material for drug substance synthesis. Hydroxyestradienone has four stereogenic centers leading to 8 diastereomers and 16 enantiomers of which only six diastereomers were synthetically accessible but two not. A computational multistep protocol resulting in density functional P2PLYP-D3(BJ)/dev2-TZVPP Gibbs free energies and SMD solvation free energies led to a clear separation between the existing and the synthetically not accessible enantiomers, whereas multiple geometry-based and cheminformatic descriptors were not able to explain experimental findings.

Self-Assembly, Adaptive Response, and in,out-Stereoisomerism of Large Orthoformate Cryptands.

We report on triethylene glycol-based orthoformate cryptands, which adapt their bridgehead configurations in response to metal templates and intramolecular hydrogen bonding in a complex manner. In contrast to smaller 1.1.1-orthoformate cryptands, the inversion from out,out-2.2.2 to in,in-2.2.2 occurs spontaneously by thermal homeomorphic isomerization, i. e., without bond breakage. The global thermodynamic minimum of the entire network, which includes an unprecedented third isomer (in,out-2.2.2), could only be reached under conditions that facilitate dynamic covalent exchange. Both inversion processes were studied in detail, including DFT calculations and MD simulations, which were particularly helpful for explaining differences between equilibrium compositions in solvents chloroform and acetonitrile. Unexpectedly, the system could be driven to the in,out-2.2.2 state by using a metal template with a size mismatch with respect to the out,out-2.2.2 cage.

The effect of stereoisomerism on the 4D-QSAR study of some dipeptidyl boron derivatives.

The electron conformational genetic algorithm (EC-GA) method had been employed by distinguishing between enantiomers for the first time as a 4D-QSAR approach to reveal the pharmacophore (Pha) and to predict the bioactivity of the dipeptidyl boron compounds. The Electron Conformational Matrices of Congruity (ECMCs) were prepared for all conformers of compounds in the data set based on the quantum chemical calculations at HF/3-21 G level in an aqueous medium. The comparison of the ECMCs within the certain tolerances by the EMRE program revealed the pharmacophore for some dipeptidyl boron derivatives. For the selection of the most influential parameters on the activity and the calculation of theoretical activities, the genetic algorithm with the non-linear least square method was used. The final model was validated by the cross-validation method with the division of the data set into training and test items. The 12-parameter model gave excellent statistical results (R2training = 0.850, R2test = 0.809, q2 = 0.755, q2ext1 = 0.776, q2ext2 = 0.759, q2ext3 = 0.735, CCCtr = 0.922, CCCtest = 0.846, CCCall = 0.905). Because of the inexistence of 4D-QSAR studies on the dipeptidyl boron derivatives and the stereoisomerism effect on the biological activity was examined for the first time for these compounds, this study plays an important role in the development of new boron-containing compounds.

Tetrahedral Pegs in Square Holes: Stereochemistry of Diboron Porphyrazines and Phthalocyanines.

The first examples of diboron complexes of the tetrapyrroles octaethylporphyrazine (OEPz) and 2,9,16,23-tetra-t-butyl-phthalocyanine (Pc) are reported, counterpoints to the better known monoboron tripyrroles, subporphyrazine and subphthalocyanine. Two stereochemical possibilities are observed, with cisoid-B2 OF2 (OEPz), both cisoid-B2 OPh2 (OEPz) and transoid-B2 OPh2 (OEPz), transoid-B2 OF2 (Pc) and cisoid-B2 OPh2 (Pc) having been isolated and characterised, including structure determinations for the OEPz complexes. This variation in stereochemistry, which can be extended to include the previously reported transoid-B2 OF2 (porphyrin), cisoid-[B2 OF2 (corrole)]- , and both transoid- and cisoid-B2 OF2 (calixphyrin), prompted a wider DFT study to elucidate the factors influencing the stereochemical preferences. This shows that the cisoid/transoid preference is correlated to the ease with which the macrocycle accommodates a rectangularly distorted N4 cavity.

An Exceptionally Close, Non-Bonded Hydrogen-Hydrogen Contact with Strong Through-Space Spin-Spin Coupling.

Condensation of 1,8,13-tris(mercaptomethyl)triptycene and tris(bromomethyl)methane yields an in,in-cyclophane with two inwardly directed methine groups. Based on X-ray analysis and DFT and MP2 calculations, the hydrogen-hydrogen non-bonded contact distance is estimated to be 1.50-1.53 Å. Furthermore, the two in-hydrogen atoms show obvious spin-spin coupling with J=2.0 Hz.

Searching for stereoisomerism in crystallographic databases: algorithm, analysis and chiral curiosities.

The automated identification of chiral centres in molecular residues is a non-trivial task. Current tools that allow the user to analyze crystallographic data entries do not identify chiral centres in some of the more complex ring structures, or lack the possibility to determine and compare the chirality of multiple structures. This article presents an approach to identify asymmetric C atoms, which is based on the atomic walk count algorithm presented by Rücker & Rücker [(1993), J. Chem. Inf. Comput. Sci. 33, 683-695]. The algorithm, which we implemented in a computer program named ChiChi, is able to compare isomeric residues based on the chiral centres that were identified. This allows for discrimination between enantiomers, diastereomers and constitutional isomers that are present in crystallographic databases. ChiChi was used to process 254 354 organic entries from the Cambridge Structural Database (CSD). A thorough analysis of stereoisomerism in the CSD is presented accompanied by a collection of chiral curiosities that illustrate the strength and versatility of this approach.

Stereoisomerism, crystal structures, and dynamics of belt-shaped cyclonaphthylenes.

The chemistry of a belt-shaped cyclic array of aromatic panels, a so-called "nanohoop," has increasingly attracted much interest, partly because it serves as a segmental model of single-wall carbon nanotubes with curved sp(2)-carbon networks. Although the unique molecular structure of nanohoops is expected to deepen our understanding in curved π-systems, its structural chemistry is still in its infancy despite structural variants rapidly accumulated over the past several years. For instance, structural characteristics that endow the belt shapes with rigidity, an important structural feature relevant to carbon nanotubes, have not been clarified to date. We herein report the synthesis and structures of a series of belt-shaped cyclonaphthylenes. Random synthesis methods using three precursor units with different numbers of naphthylene panels allowed us to prepare 6 congeners consisting of 6 to 11 naphthylene panels, and relationships between the rigidity and the panel numbers, i.e., molecular structures, were investigated. Fundamental yet complicated stereoisomerism in the belt-shaped structures was disclosed by mathematical methods, and dynamics in the panel rotation was revealed by dynamic NMR studies with the aid of theoretical calculations.

Preclinical Evaluation of [(18)F]THK-5105 Enantiomers: Effects of Chirality on Its Effectiveness as a Tau Imaging Radiotracer.

PURPOSE: Noninvasive imaging of tau and amyloid-ß pathologies would facilitate diagnosis of Alzheimer's disease (AD). Recently, we have developed [(18)F]THK-5105 for selective detection of tau pathology by positron emission tomography (PET). The purpose of this study was to clarify biological properties of optically pure [(18)F]THK-5105 enantiomers. PROCEDURES: Binding for tau aggregates in AD brain section was evaluated by autoradiography (ARG). In vitro binding assays were performed to evaluate the binding properties of enantiomers for AD brain homogenates. The pharmacokinetics in the normal mouse brains was assessed by ex vivo biodistribution assay RESULTS: The ARG of enantiomers showed the high accumulation of radioactivity corresponding to the distribution of tau deposits. In vitro binding assays revealed that (S)-[(18)F]THK-5105 has slower dissociation from tau than (R)-[(18)F]THK-5105. Biodistribution assays indicated that (S)-[(18)F]THK-5105 eliminated faster from the mouse brains and blood compared with (R)-[(18)F]THK-5105. CONCLUSION: (S)-[(18)F]THK-5105 could be more suitable than (R)-enantiomer for a tau imaging agent.

Diagnostic value of serum ferritin, alpha-fetoprotein and alpha-fetoprotein-L3 alone or in combination for diagnosis of primary hepatic carcinoma / 中华检验医学杂志

Objective To investigate the diagnostic value of serum FER, AFP and AFP-L3 alone or in combination for diagnosis of primary hepatic carcinoma( PHC).Methods This was a case-control study. Serum FER, AFP and AFP-L3 were determined in 212 patients with PHC ( StageⅠ45 cases, StageⅡ78 cases, StageⅢ81 cases, StageⅣ8 cases) , 127 patients with cirrhosis, 101 patients with chronic hepatitis and 98 controls in the Beijing Youan Hospital affiliated to Capital Medical University from January 2014 to December 2014.Levels of FER, AFP and AFP-L3 were measured by chemiluminescence, while serum samples were pre-treatment with affinity adsorption before AFP-L3 detection.FER, AFP and AFP-L3 levels were analyzed using the nonparametric Wilcoxon test among all groups.Diagnostic performance were analyzed among the groups with the three biomarkers independently and combined.Logistic regression, plotted ROC curve and calculated the area under ROC curve ( AUC) were applied to assess the diagnostic value of each index.Results Serum concentration of FER in PHC, cirrhosis, chronic hepatitis groups and healthy controls were 308.45 ( 148.98 -662.80 ) , 151.70 ( 51.44 -507.40 ) , 298.20 ( 157.30 -701.80 ) , 113.50( 54.98-221.38) μg/L, respectively.The concentration of AFP were 48.50(5.25 -748.40), 3.91(1.80-17.53), 4.76 (2.29-30.56), 2.57 (0.93-3.68) μg/L in each group.The serum levels of AFP-L3 in each group were 4.75(0.61-127.95), 0.61 (0.61-2.50), 0.61 (0.61-2.85), 0.61 (0.61-0.61) μg/L.The concentration of FER, AFP and AFP-L3 differs statistically in PHC, cirrhosis, chronic hepatitis group and healthy controls (χ2 =67.66,146.31,119.02,P<0.001).The content of serum FER, AFP and AFP-L3 increased gradually as the stage level aggravating ( StageⅠ-Ⅳ) , there was significant differences among groups (χ2 =21.63,22.68,21.98, P<0.001) .When using one serum marker, FER had the highest sensitivity (75.00%) , while AFP-L3 had the highest specificity (82.52%). While using two serum markers, FER/AFP had the highest sensitivity (89.15%) , FER+AFP-L3 and AFP+AFP-L3 had a higher specificity (86.20%).The combined detection of FER/AFP/AFP-L3 improved the sensitivity of the test to 89.15%, while FER+AFP+AFP-L3 had a specificity of 86.50%.The AUC of combination of FER, AFP and AFP-L3 was 0.803 ±0.019 (95% CI:0.765-0.841), which was higher than the AUC of either FER(0.748 ±0.022,95% CI:0.705-0.790, Z=4.67,P<0.001) and AFP-L3 (0.726 ±0.024,95% CI: 0.679 -0.772, Z=3.64,P<0.001).However, there was no significant difference in AUC between AFP alone ( 0.776 ±0.021, 95% CI: 0.735 -0.818 ) and the combined detection ( Z=1.34, P=0.18 ) .Conclusions FER was a potential marker for PHC diagnosis.The combination of FER, AFP and AFP-L3 has higher value of clinical applications than one of them independently.

Stereoisomerism effect on sugar-lectin binding of self-assembled glyco-nanoparticles of linear and brush copolymers.

Binding behavior of carbohydrate and protein is known to be crucial to the biological roles of sugars. Recently, we notice that, even to the same lectin, some reported binding results based on glycopolymers and/or self-assembled glyco-nanoparticles are different from those obtained on small molecular level. Some of such discrepancy could be associated with the different detection methods used. In this paper, by using self-assembled nanoparticles based on brush and linear glycopolymers, this stereoisomerism effect was evaluated systematically, both in solution and on solution-solid interface by different methods. All measurements led to the same conclusion that the stereoisomer of sugars determined the binding ability of glyco-nanoparticles with different lectins. The investigation also provided evidence on the different binding modes of nanoparticles of linear polymers and brush polymers.

Estudo comparativo entre bupivacaína (S75-R25) e ropivacaína para avaliar a segurança cardiovascular em bloqueio do plexo braquial / Comparative study related to cardiovascular safety between bupivacaine (S75-R25) and ropivacaine in brachial plexus block / Estudio comparativo entre la bupivacaína (S75-R25) y la ropivacaína para evaluar la seguridad cardiovascular en el bloqueo del plexo braquial

JUSTIFICATIVA E OBJETIVOS: Bupivacaína é o fármaco de escolha para anestesia regional por causa da eficácia, longa duração e do bloqueio motor menos intenso. Bupivacaína (S75-R25) é uma mistura de isômeros ópticos que contém 75% de levobupivacaína (S-) e 25% de dextrobupivacaína (R+) e foi criada por uma companhia farmacêutica brasileira. Este estudo comparou a eficácia e segurança de bupivacaína S75-R25 com vasoconstritor e ropivacaína para o sistema cardiovascular em bloqueio do plexo braquial. MÉTODOS: Pacientes foram randomizados para receber bloqueio do plexo braquial com bupivacaína S75-R25 (Grupo B) com epinefrina 1:200.000 ou ropivacaína (Grupo R), ambos os fármacos a 0,50%, em 30 mL ECG contínuo (Holter) foi registrado durante todo o procedimento, bem como a escala de força de Lovett, além de monitoramento (frequência cardíaca, oximetria de pulso e pressão arterial não invasiva). A incidência de eventos adversos foi comparada com os testes do qui-quadrado ou exato de Fisher. RESULTADOS: Quarenta e quatro pacientes foram estudados. Não houve diferença significativa em relação à idade, peso, altura, gênero e tempo cirúrgico. Não houve diferença entre arritmias supraventriculares antes ou depois do bloqueio do plexo braquial, independentemente do anestésico local escolhido. A perda de sensibilidade foi mais rápida no Grupo B (23,1 ± 11,7 min) em comparação com o Grupo R (26,8 ± 11,5 min), embora não significativa (p = 0,205, teste t de Student). Houve uma redução da frequência cardíaca, observada durante a monitoração contínua de 24 horas (Holter). CONCLUSÃO: Este estudo demonstrou eficácia semelhante entre bupivacaína S75-R25 e ropivacaína para bloqueio do plexo braquial, com incidências semelhantes de arritmias supraventriculares.

BACKGROUND AND OBJECTIVES: Bupivacaine is a first choice for regional anesthesia considering its effectiveness, long duration and less motor blockade. Bupivacaine (S75-R25) is a mixture of optical isomers containing 75% levobupivacaine (S-) and 25% dextrobupivacaine (R+) created by a Brazilian pharmaceutical company. This investigation compared cardiac safety and efficacy of bupivacaine S75-R25 with vasoconstrictor and ropivacaine for brachial plexus blockade. METHODS: Patients were randomized to receive brachial plexus anesthesia with either bupivacaine S75-R25 with epinephrine 1:200,000 (bupi) or ropivacaine (ropi), both at 0.50%, in 30 mL solution. We registered a continuous Holter ECG throughout the procedure, as well as the Lovett scale of force in addition to monitoring (heart rate, pulse oximetry and non-invasive blood pressure). The incidence of adverse events was compared with the chi-square or Fisher test. RESULTS: We allocated forty-four patients into two groups. They did not show any difference related to age, weight or height, gender, as well as for surgical duration. Supraventricular arrhythmias were not different before or after the plexus blockade, independent of the local anesthetic chosen. Loss of sensitivity was faster for the bupivacaine group (23.1 ± 11.7 min) compared to the ropivacaine one (26.8 ± 11.5 min), though not significant (p = 0.205, Student t). There was a reduction in the cardiac rate, observed during the twenty-four-hour Holter monitoring. CONCLUSIONS: This study showed similar efficacy between bupivacaine S75-R25 for brachial plexus blockade and ropivacaine, with similar incidences of supraventricular arrhythmias.

JUSTIFICATIVA Y OBJETIVOS: La Bupivacaína es el fármaco por elección para la anestesia regional por poseer una eficacia, una larga duración y un bloqueo motor menos intenso. La Bupivacaína (S75-R25) consiste en una mezcla de isómeros ópticos que contienen un 75% de levobupivacaína (S-) y un 25% de dextrobupivacaína (R+), y fue creada por una compañía farmacéutica brasileña. Este estudio comparó la eficacia y la seguridad de la bupivacaína S75-R25 con el vasoconstrictor y la ropivacaína para el sistema cardiovascular en el bloqueo del plexo braquial. MÉTODOS: El equipo de investigación colocó de forma aleatoria a los pacientes que recibirían el bloqueo del plexo braquial con la bupivacaína S75-R25 (Grupo B) o la ropivacaína (Grupo R), ambos fármacos al 0,50%, y 30 mL de epinefrina 1:200.000. El ECG continuo (Holter) se registró durante todo el procedimiento, como también la escala de fuerza de Lovett, además de la monitorización (frecuencia cardíaca, oximetría de pulso y presión arterial no invasiva). La incidencia de eventos adversos fue comparada con los test del Xi-Cuadrado (Xi²) o exacto de Fisher. RESULTADOS: Fueron divididos en dos grupos 44 pacientes. No hubo diferencia significativa con relación a la edad, peso, altura, sexo y tiempo de operación. No hubo diferencia entre las arritmias supraventriculares antes o después del bloqueo del plexo braquial, independientemente del anestésico local elegido. La pérdida de sensibilidad fue más rápida en el Grupo B (23,1 ± 11,7 min) en comparación con el Grupo R (26,8 ± 11,5 min), aunque no fuere significativa (p = 0,205, test t de Student). Hubo una reducción de la frecuencia cardíaca, observada durante la monitorización continua de 24 horas (Holter). CONCLUSIONES: Este estudio demostró una eficacia parecida entre la bupivacaína S75-R25 y la ropivacaína para el bloqueo del plexo braquial, con incidencias parecidas de arritmias supraventriculares.