Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 654
Filtrar
1.
Biochem Biophys Res Commun ; 534: 107-113, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33316543

RESUMO

Measurement of autophagic flux in vivo is critical to understand how autophagy can be used to combat disease. Neurodegenerative diseases have a special relationship with autophagy, which makes measurement of autophagy in the brain a significant research priority. Currently, measurement of autophagic flux is possible through use of transgenic constructs, or application of a lysosomal inhibitor such as chloroquine. Unfortunately, chloroquine is not useful for measuring autophagic flux in the brain and the use of transgenic animals necessitates cross-breeding of transgenic strains and maintenance of lines, which is costly. To find a drug that could block lysosomal function in the brain for the measurement of autophagic flux, we selected compounds from the literature that appeared to have similar properties to chloroquine and tested their ability to inhibit autophagic flux in cell culture and in mice. These chemicals included chloroquine, quinacrine, mefloquine, promazine and trifluoperazine. As expected, chloroquine blocked lysosomal degradation of the autophagic protein LC3B-II in cell culture. Quinacrine also inhibited autophagic flux in cell culture. Other compounds tested were not effective. When injected into mice, chloroquine caused accumulation of LC3B-II in heart tissue, and quinacrine was effective at blocking LC3B-II degradation in male, but not female skeletal muscle. None of the compounds tested were useful for measuring autophagic flux in the brain. During this study we also noted that the vehicle DMSO powerfully up-regulated LC3B-II abundance in tissues. This study shows that chloroquine and quinacrine can both be used to measure autophagic flux in cells, and in some peripheral tissues. However, measurement of flux in the brain using lysosomal inhibitors remains an unresolved research challenge.


Assuntos
Autofagia/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cloroquina/farmacologia , Lisossomos/efeitos dos fármacos , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Células HeLa , Humanos , Lisossomos/metabolismo , Macrolídeos/farmacologia , Masculino , Mefloquina/farmacologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/metabolismo , Promazina/farmacologia , Quinacrina/farmacologia , Trifluoperazina/farmacologia
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 119012, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33039847

RESUMO

Detection and qualification process related to impurities assume importance in pharmacological drug development programmes and the present article gives the structural and spectral characterisation of phenothiazine derivatives, promazine (PME) and trifluoperazine (TPE) and their self-assembly with graphene/fullerene/carbon ring (CG/CF/CR) systems theoretically. The investigation of adsorption behaviour of these compounds can provide valuable information about its reactivity, electronic and structural properties. Three-dimensional electrostatic potential diagrams were mapped. The frontier orbital energies and energy band gaps of the molecules were computed. Delocalization of charge density between the bonding or lone pair and antibonding orbitals is calculated by NBO analysis. Docking was executed to investigate binding areas of chemical compounds. Bioactivity scores show that the pharmacokinetic and pharmacological properties of the ligands are appropriate leading to be considered potential drug agents. The obtained theoretical wavenumber results of the present study were fully compatible with the experimental results.


Assuntos
Fulerenos , Grafite , Adsorção , Promazina , Psicotrópicos , Teoria Quântica , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Trifluoperazina
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 227: 117563, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31689607

RESUMO

Phenothiazines are very effective antipsychotic drugs, which also have anticancer and antimicrobial activities. Despite being used in human treatment, the molecular mechanism of the biological actions of these molecules is not yet understood in detail. The role of the interactions between phenothiazines and proteins or lipid membranes has been much discussed. Herein, fourier-transform infrared (FTIR) spectroscopic studies were used to investigate the effect of three phenothiazines: fluphenazine (FPh); chlorpromazine (ChP); and propionylpromazine (PP) on the structures of a positively charged poly-l-lysine (PLL) peptide, a negatively charged dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol (DPPC/DPPG) membrane, and on the mutual interactions between electrostatically associated PLL molecules and DPPC/DPPG membranes. Phenothiazine-induced alterations in the secondary structure of PLL, the conformational state (trans/gauche) of the hydrocarbon lipid chains, and the hydration of the DPPC/DPPG membrane interface were studied on the basis of amide I' vibrations, antisymmetric and symmetric stretching vibrations of the CH2 groups of the lipid hydrocarbon chains (νsCH2), and stretching vibrations of the lipid C=O groups (νC = O), respectively. It was shown that in the presence of negatively charged DPPC/DPPG membranes, the phenothiazines were able to modify the secondary structure of charged PLL molecules. Additionally, the effect of PLL on the structure of DPPC/DPPG membranes was also altered by the presence of the phenothiazine molecules.


Assuntos
1,2-Dipalmitoilfosfatidilcolina/metabolismo , Antipsicóticos/farmacologia , Clorpromazina/farmacologia , Flufenazina/farmacologia , Fosfatidilgliceróis/metabolismo , Promazina/análogos & derivados , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Humanos , Polilisina/metabolismo , Promazina/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
5.
Addict Behav ; 60: 53-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27088514

RESUMO

A 24-year old woman with multisubstance use since the age of 13, including opioids and cocaine, and long-standing HIV/HCV seropositivity status, presented with psychosis, agitation, and insomnia at the emergency department of a university hospital. She had been abusive and physically aggressive frequently without specific reasons and was involved in criminal legal cases. She was hospitalized twice. During her first hospital stay she experienced a brief episode of detachment from her environment, similar to episodes reportedly suffered at home. Psychosis had developed following heavy polysubstance abuse. Her mother provided sachets containing benzylglycinamide, a substance with no known psychotropic effects, which were also present in the patient's urine. She was occasionally positive for cannabinoids. She used to buy various novel psychoactive substances (NPSs) from the internet and used experimentally various substances freely made available to her by drug suppliers/dealers. She was unable to explain clearly why she was taking any of the identified NPS. She stated she was taking benzylglycinamide to calm her when smoking synthetic cannabinoids. While it appears that benzylglycinamide is not likely to constitute a novel drug of abuse, her polysubstance use exemplifies trends in NPS use patterns among the youths in the Western world and should alert mental health workers as to the possible dangers of such behavior and its reflection on social behavior and psychopathology.


Assuntos
Glicina/análogos & derivados , Infecções por HIV/complicações , Psicoses Induzidas por Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Ansiolíticos/uso terapêutico , Antirretrovirais/uso terapêutico , Antipsicóticos/uso terapêutico , Feminino , Glicina/sangue , Glicina/urina , Infecções por HIV/tratamento farmacológico , Humanos , Drogas Ilícitas/sangue , Drogas Ilícitas/urina , Itália , Lorazepam/uso terapêutico , Palmitato de Paliperidona/uso terapêutico , Promazina/uso terapêutico , Psicoses Induzidas por Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/urina , Adulto Jovem
6.
Eur J Pharm Sci ; 83: 36-44, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26690045

RESUMO

The feasibility of titanium dioxide (TiO2) photocatalysis, electrochemically assisted Fenton reaction (EC-Fenton) and direct electrochemical oxidation (EC) for simulation of phase I metabolism of drugs was studied by comparing the reaction products of buspirone, promazine, testosterone and 7-ethoxycoumarin with phase I metabolites of the same compounds produced in vitro by human liver microsomes (HLM). Reaction products were analysed by UHPLC-MS. TiO2 photocatalysis simulated the in vitro phase I metabolism in HLM more comprehensively than did EC-Fenton or EC. Even though TiO2 photocatalysis, EC-Fenton and EC do not allow comprehensive prediction of phase I metabolism, all three methods produce several important metabolites without the need for demanding purification steps to remove the biological matrix. Importantly, TiO2 photocatalysis produces aliphatic and aromatic hydroxylation products where direct EC fails. Furthermore, TiO2 photocatalysis is an extremely rapid, simple and inexpensive way to generate oxidation products in a clean matrix and the reaction can be simply initiated and quenched by switching the UV lamp on/off.


Assuntos
Buspirona/química , Cumarínicos/química , Promazina/química , Testosterona/química , Titânio/química , Buspirona/metabolismo , Catálise , Cumarínicos/metabolismo , Remoção de Radical Alquila , Eletroquímica , Humanos , Hidrogenação , Hidroxilação , Ferro/química , Microssomos Hepáticos/metabolismo , Oxirredução , Promazina/metabolismo , Testosterona/metabolismo , Titânio/efeitos da radiação , Raios Ultravioleta
7.
Anal Chem ; 87(4): 2242-8, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25615803

RESUMO

The effects of medicine on the biomolecular interaction have been given increasing attention in biochemistry and affinity-based analytics since the environment in vivo is complex especially for the patients. Herein, myoglobin, a biomarker of acute myocardial infarction, was used as a model, and the medicine effects on the interactions of myoglobin/aptamer and myoglobin/antibody were systematically investigated using atomic force microscopy (AFM) for the first time. The results showed that the average binding force and the binding probability of myoglobin/aptamer almost remained unchanged after myoglobin-modified gold substrate was incubated with promazine, amoxicillin, aspirin, and sodium penicillin, respectively. These parameters were changed for myoglobin/antibody after the myoglobin-modified gold substrate was treated with these medicines. For promazine and amoxicillin, they resulted in the change of binding force distribution of myoglobin/antibody (i.e., from unimodal distribution to bimodal distribution) and the increase of binding probability; for aspirin, it only resulted in the change of the binding force distribution, and for sodium penicillin, it resulted in the increase of the average binding force and the binding probability. These results may be attributed to the different interaction modes and binding sites between myoglobin/aptamer and myoglobin/antibody, the different structures between aptamer and antibody, and the effects of medicines on the conformations of myoglobin. These findings could enrich our understanding of medicine effects on the interactions of aptamer and antibody to their target proteins. Moreover, this work will lay a good foundation for better research and extensive applications of biomolecular interaction, especially in the design of biosensors in complex systems.


Assuntos
Anticorpos/química , Aptâmeros de Nucleotídeos/química , Microscopia de Força Atômica , Mioglobina/química , Amoxicilina/química , Amoxicilina/farmacologia , Anticorpos/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , Aspirina/química , Aspirina/farmacologia , Sítios de Ligação/efeitos dos fármacos , Biomarcadores/química , Biomarcadores/metabolismo , Ouro/química , Mioglobina/metabolismo , Penicilina G/química , Penicilina G/farmacologia , Promazina/química , Promazina/farmacologia , Ligação Proteica/efeitos dos fármacos
9.
Int J Pharm ; 475(1-2): 270-81, 2014 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-25148730

RESUMO

Phenothiazine drugs - chlorpromazine (CPZ), promazine (PZ) and promethazine (PMZ) - were exposed to 266 nm (fourth harmonic of the Nd:YAG pulsed laser radiation) in order to be modified at molecular level and to produce an enhancement of their antibacterial activity. The irradiated samples were analysed by several methods: pH and surface tension measurements, UV-vis-NIR absorption spectroscopy, laser induced fluorescence and thin layer chromatography. The purpose of these investigations was to study and describe the modified properties of the medicines to further investigate their specific interactions with materials such as cotton, polyester and Parafilm M as a model smooth surface. The textile materials may be impregnated with phenothiazines drug solutions exposed to laser radiation in order to be used in treatments applied on the surface of the organism. Some of the phenothiazines solutions exposed prolonged time intervals to laser radiation have much better activity against several bacteria. Therefore, in the paper, it is reported the wetting behaviour of CPZ, PZ and PMZ solutions, irradiated for time intervals between 1 and 240 min, on the surfaces of the three textures in order to draw a conclusion about their wettability as a function of time.


Assuntos
Fenotiazinas/química , Soluções/química , Antibacterianos/química , Clorpromazina/química , Cromatografia em Camada Delgada/métodos , Fibra de Algodão , Concentração de Íons de Hidrogênio , Lasers , Parafina/química , Poliésteres/química , Promazina/química , Prometazina/química , Tensão Superficial , Molhabilidade
10.
Talanta ; 125: 1-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24840407

RESUMO

The development of a field-amplified sample stacking technique is presented. Sensitivity enhancement in this technique was obtained by repetitive injections of a sample followed by steps of sample matrix removal through the application of counter-pressure. Under optimized conditions the background electrolyte (BGE) was composed of 80 mM H3PO4 while the sample matrix contained 0.5mM H3PO4 and 30% (v/v) methanol. The elaborated method enabled a 4-fold effective injection of the sample (53 s, 0.5 psi). Each injection was followed by a focusing step during which the application of a voltage (2 kV) and counter-pressure (-1 psi) was performed for 0.65 min. The method was developed for the determination of six psychiatric drugs (opipramol, hydroxyzine, promazine, amitriptyline, fluoxetine, and thioridazine). The elaborated method was applied for analysis of human urine samples after a simple liquid-liquid extraction procedure. The detection limits obtained were in the range of 2.23-6.21 ng/mL.


Assuntos
Urinálise/métodos , Amitriptilina/urina , Antidepressivos Tricíclicos/urina , Calibragem , Cátions , Eletrólitos , Eletroforese , Eletroforese Capilar , Fluoxetina/urina , Humanos , Concentração de Íons de Hidrogênio , Hidroxizina/urina , Limite de Detecção , Opipramol/urina , Ácidos Fosfóricos/química , Pressão , Promazina/urina , Solventes/química , Temperatura , Tioridazina/urina
11.
Structure ; 22(2): 291-303, 2014 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-24373770

RESUMO

Conformational transitions of the cellular form of the prion protein, PrP(C), into an infectious isoform, PrP(Sc), are considered to be central events in the progression of fatal neurodegenerative diseases known as transmissible spongiform encephalopathies. Tricyclic phenothiazine compounds exhibit antiprion activity; however, the underlying molecular mechanism of PrP(Sc) inhibition remains elusive. We report the molecular structures of two phenothiazine compounds, promazine and chlorpromazine bound to a binding pocket formed at the intersection of the structured and the unstructured domains of the mouse prion protein. Promazine binding induces structural rearrangement of the unstructured region proximal to ß1, through the formation of a "hydrophobic anchor." We demonstrate that these molecules, promazine in particular, allosterically stabilize the misfolding initiator-motifs such as the C terminus of α2, the α2-α3 loop, as well as the polymorphic ß2-α2 loop. Hence, the stabilization effects of the phenothiazine derivatives on initiator-motifs induce a PrP(C) isoform that potentially resists oligomerization.


Assuntos
Fenotiazinas/química , Príons/química , Sítio Alostérico , Motivos de Aminoácidos , Animais , Sítios de Ligação , Clorpromazina/química , Camundongos , Simulação de Dinâmica Molecular , Promazina/química , Ligação Proteica , Desnaturação Proteica , Dobramento de Proteína , Isoformas de Proteínas/química , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína
12.
Bioorg Med Chem Lett ; 23(16): 4587-90, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23856051

RESUMO

Both pharmacophore models of the human ether-à-go-go-related gene (hERG) channel blockers and phospholipidosis (PLD) inducers contain a hydrophobic moiety and a hydrophilic motif/positively charged center, so it is interesting to investigate the overlap between the ligand chemical spaces of both targets. We have assayed over 4000 non-redundant drug-like compounds for both their hERG inhibitory activity and PLD inducing potential in a quantitative high throughput screening (qHTS) format. Seventy-seven percent of PLD inducing compounds identified from the screening were also found to be hERG channel blockers, and 96.9% of the dually active compounds were positively charged. Among the 48 compounds that induced PLD without inhibiting hERG channel, 24 compounds (50.0%) carried steroidal structures. According to our results, hERG channel blockers and PLD inducers share a large chemical space. In addition, a positively charged hERG channel blocker will most likely induce PLD, while a steroid PLD inducer is less likely a hERG channel blocker.


Assuntos
Lipidoses/induzido quimicamente , Fosfolipídeos/metabolismo , Antipsicóticos/química , Antipsicóticos/farmacologia , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Humanos , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Fosfolipídeos/química , Promazina/química , Promazina/metabolismo , Promazina/farmacologia , Relação Quantitativa Estrutura-Atividade , Esteroides/química
13.
Colloids Surf B Biointerfaces ; 103: 496-501, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23261572

RESUMO

In this paper we report the effect of two cationic (imipramine hydrochloride (IMP) and promazine hydrochloride (PMZ)) and one anionic (sodium salt of ibuprofen (IBF)) drugs on the clouding behavior of a nonionic polymer hydroxypropyl methyl cellulose (HPMC). Though all the three drugs increase the cloud point (CP) of HPMC, the effect was found to be minimum in the case of IBF. Further, the effect of adding salts (NaF, NaCl, NaBr, NaNO(3), Na(2)SO(4), Na(3)PO(4), KCl, KBr, KNO(3)) in the presence of amphiphilic drugs (IMP and PMZ) on the CP of HPMC was seen. Almost linear decrease in the CP was observed with the [salt] at fixed concentrations of these drugs whereas in the absence of drugs the decrement in the CP was slight. The energetic parameters (ΔG(c)(0), ΔH(c)(0) and TΔS(c)(0)) were evaluated and it implies that the disruption of water structure becomes significantly prominent at lower concentrations of the drugs at fixed salt concentrations.


Assuntos
Metilcelulose/análogos & derivados , Preparações Farmacêuticas/química , Sais/química , Tensoativos/química , Ânions , Derivados da Hipromelose , Ibuprofeno/química , Imipramina/química , Metilcelulose/química , Micelas , Modelos Moleculares , Promazina/química , Soluções , Termodinâmica
14.
J Colloid Interface Sci ; 387(1): 194-204, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22939256

RESUMO

An evaluation of the interactions of phenothiazine tranquilizer drugs (promazine hydrochloride; PMZ and promethazine hydrochloride; PMT) with bile salts viz., sodium cholate (NaC) and sodium deoxycholate (NaDC) in aqueous medium, investigated through different physicochemical measurements is presented in this work. The mixed micellization behavior and surface properties of the phenothiazine-bile salt systems have been analyzed by conductivity and surface tension measurements. Application of different theoretical approaches to all the phenothiazine-bile salt mixtures shows a non-ideal behavior. Further, the spectroscopic techniques such as UV-visible and steady state fluorescence have been employed to study the binding of phenothiazines with bile salts. The stoichiometric ratios, binding constants (K), and free energy change (ΔG) for the phenothiazine-bile salt complexes were estimated from the Benesi-Hildebrand (B-H) double reciprocal plots obtained by using the changes in spectral intensities of phenothiazines on addition of bile salts. The results are discussed in the light of use of bile salts as promising drug delivery agents for phenothiazines and hence improve their bioavailabilty.


Assuntos
Ácido Desoxicólico/metabolismo , Promazina/metabolismo , Prometazina/metabolismo , Colato de Sódio/metabolismo , Tranquilizantes/metabolismo , Micelas , Termodinâmica
15.
Bioorg Med Chem Lett ; 22(16): 5308-12, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22789428

RESUMO

N-(4-chlorobenzyl)triflupromazinium chloride, a known antitubercular agent, has been found to also be active against HSV-1. A preliminary structure-activity relation has been explored to determine which groups are crucial to viral inhibition. Antiviral assessments such as GFP reduction, plaque reduction, treatment timing and wash-out studies have also been probed to determine a mode of action for QPD-1. Based on this preliminary data, it appears that QPD-1 is a reversible inhibitor, suspected to inhibit early stages of viral replication of HSV-1 at 50 µM, equipotent to acyclovir.


Assuntos
Antivirais/síntese química , Herpesvirus Humano 1/efeitos dos fármacos , Fenotiazinas/síntese química , Promazina/química , Compostos de Amônio Quaternário/síntese química , Aciclovir/farmacologia , Animais , Antivirais/química , Antivirais/farmacologia , Chlorocebus aethiops , Humanos , Fenotiazinas/química , Fenotiazinas/farmacologia , Promazina/síntese química , Promazina/farmacologia , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Relação Estrutura-Atividade , Células Vero , Replicação Viral/efeitos dos fármacos
16.
Artigo em Inglês | MEDLINE | ID: mdl-22750346

RESUMO

To know the interaction of amphiphilic drugs nortriptyline hydrochloride (NOT) and promazine hydrochloride (PMZ) with serum albumins (i.e., human serum albumin (HSA) and bovine serum albumin (BSA)), techniques of UV-visible, fluorescence, and circular dichroism (CD) spectroscopies are used. The binding affinity is more in case of PMZ with both the serum albumins. The quenching rate constant (k(q)) values suggest a static quenching process for all the drug-serum albumin interactions. The UV-visible results show that the change in protein conformation of PMZ-serum albumin interactions are more prominent as compared to NOT-serum albumin interactions. The CD results also explain the conformational changes in the serum albumins on binding with the drugs. The increment in %α-helical structure is slightly more for drug-BSA complexes as compared to drug-HSA complexes.


Assuntos
Nortriptilina/metabolismo , Preparações Farmacêuticas/metabolismo , Promazina/metabolismo , Soroalbumina Bovina/metabolismo , Tensoativos/metabolismo , Adsorção , Animais , Sítios de Ligação , Bovinos , Dicroísmo Circular , Humanos , Cinética , Nortriptilina/química , Preparações Farmacêuticas/química , Promazina/química , Estrutura Secundária de Proteína , Soroalbumina Bovina/química , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Tensoativos/química
17.
Neurosci Lett ; 521(2): 115-8, 2012 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-22668855

RESUMO

Though promazine and chlorpromazine elicited cutaneous anesthesia, no study of spinal anesthesia with chlorpromazine and promazine has been reported. This study was to examine whether chlorpromazine and promazine produce spinal anesthesia. Using a rat model via intrathecal injection, we tested spinal blockades of motor function and nociception by promazine, chlorpromazine or bupivacaine, and so were dose-response studies and durations. We demonstrated that chlorpromazine and promazine elicited dose-dependent spinal blockades in motor function and nociception. On the 50% effective dose (ED(50)) basis, the rank of potency of these drugs was bupivacaine>promazine>chlorpromazine (P<0.05 for the differences). On an equipotent basis (25% effective dose [ED(25)], ED(50), and ED(75)), the block duration caused by chlorpromazine or promazine was longer than that caused by the long-lasting local anesthetic bupivacaine (P<0.01 for the differences). Chlorpromazine and promazine, as well as bupivacaine, showed longer duration of sensory block than that of motor block. Our data reported that intrathecal promazine and chlorpromazine with a more sensory-selective action over motor blockade had less potent and longer-lasting spinal blockades when compared with bupivacaine.


Assuntos
Raquianestesia/métodos , Anestésicos Locais , Clorpromazina , Promazina , Anestésicos Locais/farmacologia , Animais , Bupivacaína/farmacologia , Clorpromazina/farmacologia , Relação Dose-Resposta a Droga , Injeções Espinhais , Masculino , Atividade Motora/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Promazina/farmacologia , Ratos , Ratos Sprague-Dawley , Reflexo/efeitos dos fármacos , Punção Espinal , Vocalização Animal/efeitos dos fármacos
18.
Anal Chem ; 84(11): 4921-7, 2012 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-22540531

RESUMO

Potentiometric sensors were used to study molecular interactions in liquid environments with sensorgram methodology. This is demonstrated with a lipophilic rubber-based and a collagen-based hydrogel sensor coating. The investigated molecules were promazine and tartaric acid, respectively. The sensors were placed in a hydrodynamic wall-jet system for the recording of sensorgrams. Millivolt sensor responses were first converted to a signal, expressing the concentration of adsorbed organic ions. Using a linearization method, a pseudo-first order-kinetic model of adsorption was shown to fit the experimental results perfectly. K(assoc), k(on), and k(off) values were calculated. The technique can be used over 4 decades of concentration, and it is very sensitive to low-MW compounds as well as to multiply charged large biomolecules. This study is the first to demonstrate the application of potentiometric sensors as an alternative and complement to surface plasmon resonance methods.


Assuntos
Potenciometria/métodos , Promazina/análise , Tartaratos/análise , Adsorção , Técnicas Biossensoriais/métodos , Colágeno/química , Hidrogéis , Interações Hidrofóbicas e Hidrofílicas , Íons , Cinética , Ressonância de Plasmônio de Superfície
19.
Vet J ; 194(1): 48-54, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22534188

RESUMO

Acepromazine (ACP) is a useful therapeutic drug, but is a prohibited substance in competition horses. The illicit use of ACP is difficult to detect due to its rapid metabolism, so this study investigated the ACP metabolite 2-(1-hydroxyethyl)promazine sulphoxide (HEPS) as a potential forensic marker. Acepromazine maleate, equivalent to 30mg of ACP, was given IV to 12 racing-bred geldings. Blood and urine were collected for 7days post-administration and analysed for ACP and HEPS by liquid chromatography-mass spectrometry (LC-MS). Acepromazine was quantifiable in plasma for up to 3h with little reaching the urine unmodified. Similar to previous studies, there was wide variation in the distribution and metabolism of ACP. The metabolite HEPS was quantifiable for up to 24h in plasma and 144h in urine. The metabolism of ACP to HEPS was fast and erratic, so the early phase of the HEPS emergence could not be modelled directly, but was assumed to be similar to the rate of disappearance of ACP. However, the relationship between peak plasma HEPS and the y-intercept of the kinetic model was strong (P=0.001, r(2)=0.72), allowing accurate determination of the formation pharmacokinetics of HEPS. Due to its rapid metabolism, testing of forensic samples for the parent drug is redundant with IV administration. The relatively long half-life of HEPS and its stable behaviour beyond the initial phase make it a valuable indicator of ACP use, and by determining the urine-to-plasma concentration ratios for HEPS, the approximate dose of ACP administration may be estimated.


Assuntos
Acepromazina/farmacocinética , Antagonistas de Dopamina/farmacocinética , Medicina Legal/métodos , Cavalos/metabolismo , Acepromazina/sangue , Acepromazina/urina , Animais , Área Sob a Curva , Antagonistas de Dopamina/sangue , Antagonistas de Dopamina/urina , Meia-Vida , Cavalos/sangue , Masculino , Promazina/análogos & derivados , Promazina/sangue , Promazina/metabolismo
20.
Colloids Surf B Biointerfaces ; 95: 30-41, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22429783

RESUMO

Effect of various additives, like conventional as well as gemini cationic surfactants, non-ionic surfactants, hydrotropes, bile salts, fatty acid salts and ß-cyclodextrin on the cloud point (CP) of two amphiphilic drugs promethazine (PMT) and promazine (PMZ) hydrochlorides was investigated. These additives are generally used as pharmaceutical excipients. The CP variation with the additive concentration has been determined and the energetic parameters of the process have been estimated. All the surfactants increase the CP, while hydrotropes, bile salts and fatty acid salts, when added in low concentrations, increase or decrease, depending the added concentration, increase or decrease the CP. ß-cyclodextrin is found to decrease the CP of the drug solutions.


Assuntos
Excipientes/química , Promazina/química , Prometazina/química , Tensoativos/química , Ácidos e Sais Biliares/química , Ácidos Graxos/química , Estrutura Molecular , Termodinâmica , beta-Ciclodextrinas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...