36507-30-9Relevant academic research and scientific papers
Detection and characterization of an oxomanganese(V) porphyrin complex by rapid-mixing stopped-flow spectrophotometry
Groves, John T.,Lee, Jinbo,Marla, Sudhakar S.
, p. 6269 - 6273 (1997)
The first detection and characterization of oxomanganese(V) porphyrin complexes under ambient catalytic conditions is described. The reaction of (tetra-(N-methylpyridyl)porphyrinato)manganese(III) [Mn(III)TMPyP] with a variety of oxidants such as m-chloroperoxybenzoic acid (m-CPBA), HSO5-, and ClO- has been shown to produce the same, short-lived intermediate (1) by stopped-flow spectrophotometry. The Soret maximum of 1 was found at 443 nm, intermediate between that of oxomanganese(IV) (428 nm) and Mn(III)TMPyP (462 nm), thus facilitating its detection. The rate of formation of 1 from Mn(III)TMPyP followed second-order kinetics, first order in Mn(III) porphyrin and first order in oxidant. The rate constants have the following order: m- CPBA (2.7 x 107 M1 S1)> HSO5- 6.9 x 105 M1 s1 ? CIO (6.3 x 105 M1 s-1). Once formed, the intermediate species 1 was rapidly converted to oxoMn(IV) (2) by one-electron reduction with a first-order rate constant of 5.7 s-1. The oxoMn(IV) species 2 was relatively stable under the reaction conditions, decaying slowly to Mn(III)TMPyP with a first-order rate constant of 0.027 s-1. The identity of 1 as an oxomanganese(V) complex was indicated by its reactivity. The one-electron reduction of I to oxoMn(IV) was greatly accelerated by nitrite ion (k = 1.5 x 107 M-1 s-1). However, the reaction between nitrite and oxoMn(IV) is much slower (k = 1.4 x 102 M-1 s-1). The oxoMn(V) intermediate 1 was shown to be highly reactive toward olefins, affording epoxide products. By contrast, oxoMn(IV) (2) was not capable of effecting the same reaction under these conditions. In the presence of carbamazepine (3) efficient oxygen transfer from the highly reactive oxoMn(V) (1) to the olefin (second-order rate constant of 6.5 x 105 M-1 s-1) resulted in the conversion of I directly back to Mn(III)TMPyP without the appearance of the stable oxoMn(IV) intermediate 2. With m-CPBA as the oxidant in the presence of H218O, the product epoxide was shown to contain 35% 18O, consistent with an O-exchange-labile oxoMn(V) intermediate. Nitrite ion inhibited the epoxidation reaction competitively by one electron reduction of the oxoMn(V) intermediate to the unreactive oxoMn(IV).
Kinetic and chemical assessment of the UV/H2O2 treatment of antiepileptic drug carbamazepine
Vogna, Davide,Marotta, Raffaele,Andreozzi, Roberto,Napolitano, Alessandra,D'Ischia, Marco
, p. 497 - 505 (2004)
The UV/H2O2-induced degradation of carbamazepine, a worldwide used antiepileptic drug, recently found as contaminant in many municipal sewage treatment plant (STP) effluents and other aquatic environments, is investigated. The oxidation treatment caused an effective removal of the drug. At complete abatement of the substrate after 4 min treatment, a 35% value of removed total organic carbon (TOC) was obtained. A kinetic constant of (2.05 ± 0.14) × 109 1 mol-1 s-1 was determined for OH radical attack to carbamazepine in the UV/H2O 2 process. Preparative TLC of the reaction mixture led to the isolation of acridine-9-carboxaldehyde as a reaction intermediate. HPLC and GC/MS analysis indicated formation of small amounts of acridine, salicylic acid, catechol and anthranilic acid among the reaction products. Under the same reaction conditions, synthetically prepared 10,11-epoxycarbamazepine was easily degraded to acridine as main product, suggesting that this epoxide is a likely intermediate in the oxidative conversion of carbamazepine to acridine. Under sunlight irradiation, carbamazepine in water underwent slow degradation to afford likewise acridine as main product. In view of the mutagenic properties of acridine, these results would raise important issues concerning the possible environmental impact of carbamazepine release through domestic wastewaters and support the importance of prolonged oxidation treatments to ensure complete degradation of aromatic intermediates.
Carbamazepine oxidation catalyzed by manganese porphyrins: Effects of the β-bromination of the macrocycle and the choice of oxidant
Carvalhoda-Silva, Dayse,Mac Leod, Tatiana Cristina Oliveira,De Faria, André Luiz,Dos Santos, Joicy Santamalvina,De Carvalho, Maria Eliza Moreira Dai,Rebouas, Júlio Santos,Idemori, Ynara Marina,Assis, Marilda Das Dores
, p. 25 - 30 (2011)
Carbamazepine (CBZ), which is one of the most commonly prescribed antiepileptic drugs and also used in the treatment of trigeminal neuralgia and psychiatric disorders, is metabolized primarily by the cytochromes P450. A homologous series of β-brominated porphyrins derived from 5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrinatomanganese(III) chloride, i.e., Mn(III)(BrxTCMPP)Cl (x = 0, 2, 4, 6, and 8), was investigated as cytochrome P450 models for CBZ oxidation in CH2Cl2 by iodosylbenzene, iodobenzene diacetate, tert-butyl hydroperoxide, meta-chloroperoxybenzoic acid, and hydrogen peroxide. Unlike previous studies on metalloporphyrin-based CBZ oxidation, which yielded CBZ epoxide (CBZ-EP) as the sole product, the Mn(III)(BrxTCMPP)Cl systems catalyzed both the oxidation of CBZ to CBZ-EP and the formation of the respective vicinal diol, CBZ-DiOH. The influence of β-bromination of the macrocycle and the choice of the oxidant on the catalytic properties of the Mn(III)(BrxTCMPP)Cl (x = 0, 2, 4, 6, and 8) series were examined. Some partially β-brominated Mn-porphyrins surpass the corresponding octabrominated analogue in efficiency and selectivity, but the extent by which the β-bromination affects the catalytic activity depends on the choice of oxidant. The selectivity for CBZ oxidation to yield the respective epoxide reached 100% or ～94% by using tert-butyl hydroperoxide or hydrogen peroxide as oxygen donors, respectively.
Degradation of diclofenac, trimethoprim, carbamazepine, and sulfamethoxazole by laccase from Trametes versicolor: Transformation products and toxicity of treated effluent
Alharbi, Sultan K.,Nghiem, Long D.,van de Merwe, Jason P.,Leusch, Frederic D. L.,Asif, Muhammad B.,Hai, Faisal I.,Price, William E.
, p. 399 - 408 (2019)
The degradation of diclofenac (DCF), trimethoprim (TMP), carbamazepine (CBZ), and sulfamethoxazole (SMX) by laccase from Trametes versicolor was investigated. Experiments were conducted using the pharmaceuticals individually, or as a mixture at different initial concentrations (1.25 and 5 mg/L each). The initial enzymatic activity of all the treated samples was around 430–460 U(DMP)/L. The removal of the four selected pharmaceuticals tested individually was more effective than when tested in mixtures under the same conditions. For example, 5 mg DCF/L was completely removed to below its detection limit (1 μg/L) within 8 h in the individual experiment vs. after 24 h when dosed as a mixture with the other pharmaceuticals. A similar trend was visible with other three pharmaceuticals, with 95 vs. 39%, 82 vs. 34% and 56 vs. 49% removal after 48 h with 5 mg/L of TMP, CBZ, and SMX tested individually or as mixtures, respectively. In addition, at the lower initial concentration (1.25 mg/L each), the removal efficiency of TMP, CBZ, and SMX in mixtures was lower than that obtained at the higher initial concentrations (5 mg/L each) during both the individual and combined treatments. Four enzymatic transformation products (TPs) were identified during the individual treatments of DCF and CBZ by T. versicolor. For TMP and SMX, no major TPs were observed under the experimental conditions used. The toxicity of the solution before and after enzymatic treatment of each pharmaceutical was also assessed and all treated effluent samples were verified to be non-toxic.
Bioequivalence of carbamazepine chewable and conventional tablets: Single-dose and steady-state studies
Chan,Sawchuk,Thompson,Redalieu,Wagner Jr.,LeSher,Weeks,Hall,Gerardin
, p. 866 - 870 (1985)
Single-dose and steady-state studies were carried out on separate occasions to examine the bioequivalence of the newly formulated carbamazepine chewable tablet. In the single-dose study, the plasma levels resulting from 2 x 200-mg conventional tablets (CT), 4 x 100-mg chewable tablets swallowed whole (SW), and 4 x 100-mg chewable tablets chewed before swallowing (CHEW) were compared. A randomized 3 x 3 Latin-square design balanced for residual effects, with a 3-week washout period, was used (n = 6). Plasma samples were analyzed by a specific GC method for carbamazepine. The following parameters were used for evaluation: AUC, C(max), t(max), and t( 1/2 ). None of the parameters were significantly different except C(max) and t( 1/2 ) values for CHEW and CT. The C(max) was 25% higher and t( 1/2 ) was 11% shorter for CHEW than CT. The impact of differences in the peak plasma levels at steady state were examined by pharmacokinetic projection (400 mg b.i.d.) based on the single-dose data and with simulated induction equal to a 50% reduction in t( 1/2 ). The projected steady-state CT and CHEW plasma concentrations were similar, with a difference of only 4%. The results demonstrate the bioequivalence of the dosage forms with respect to the extent of absorption, and similar steady-state concentrations of carbamazepine in plasma can be expected. To test the conclusion from the projected study, a separate bioequivalence study to compare CHEW relative to CT was performed at steady state in normal volunteers (200 mg b.i.d.). A randomized 2 x 2 crossover design was used, with each formulation being administered for 24 d followed by a 5-d sample collection period (n = 9). The plasma samples were analyzed by a specific HPLC assay for carbamazepine (CBZ) and the epoxide metabolite (CBZE). Predose levels (days 22-24) were not significantly different for either formulation. In addition, no period effect was observed on the t( 1/2 ) of CBZ or on the metabolite fraction, indicating that induction was in a stable state and that steady state for CBZ plasma levels was reached. Again, the results demonstrate that both formulations delivered equal amounts of CBZ to the systemic circulation. The average C(max) of CBZ for CHEW was 7% higher (6.4 versus 6.0 μg/ml) and the median t(max) was slightly shorter (2.0 versus 3.0 h) than that for CT, but the differences were not significant. The results are in close agreement with those estimated in the projected study.
Interaction of cationic manganese porphyrin with G-quadruplex nucleic acids probed by differential labeling of the two faces of the porphyrin
Pradines, Vincent,Pratviel, Geneviève
, p. 2185 - 2188 (2013)
On the flip side: A free manganese porphyrin, when activated into a high-valent metal-oxo species, mediates O atom transfer (epoxidation) from both faces. This results in a mixed labeling of epoxide in labeled water. When the porphyrin (blue oval, see scheme) is bound to G-quadruplex DNA (yellow boxes), the O atom transfer reaction takes place only on the accessible face of the porphyrin. This shows the binding mode of the porphyrin to the G-quadruplex DNA. Copyright
Role of human arylacetamide deacetylase (aadac) on hydrolysis of eslicarbazepine acetate and effects of aadac genetic polymorphisms on hydrolase activity
Hirosawa, Keiya,Fukami, Tatsuki,Tashiro, Kiyomichi,Sakai, Yoshiyuki,Kisui, Fumiya,Nakano, Masataka,Nakajima, Miki
, p. 322 - 329 (2021/03/22)
Human arylacetamide deacetylase (AADAC) plays a role in the detoxification or activation of drugs and is sometimes involved in the incidence of toxicity by catalyzing hydrolysis reactions. AADAC prefers compounds with relatively small acyl groups, such as acetyl groups. Eslicarbazepine acetate, an antiepileptic drug, is a prodrug rapidly hydrolyzed to eslicarbazepine. We sought to clarify whether AADAC might be responsible for the hydrolysis of eslicarbazepine acetate. Eslicarbazepine acetatewas efficiently hydrolyzed by human intestinal and liver microsomes and recombinant human AADAC. The hydrolase activities in human intestinal and liver microsomes were inhibited by epigallocatechin gallate, a specific inhibitor of AADAC, by 82% and 88% of the control, respectively. The hydrolase activities in liver microsomes from 25 human livers were significantly correlated (r = 0.87, P a factor affecting the enzyme activity and drug response.
COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL DISORDERS
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Paragraph 0121-0122, (2016/06/01)
The invention relates to the compounds of formula I and formula IA or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I and formula IA; and methods for treating or preventing neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of epilepsy, bipolar disorder, trigeminal neuralgia, attention-deficit hyperactivity disorder (ADHD), schizophrenia, neuropathic pain, seizures, bipolar disorder, mania, phantom limb syndrome, complex regional pain syndrome, paroxysmal extreme pain disorder, neuromyotonia, intermittent explosive disorder, borderline personality disorder, Myotonia congenita and post-traumatic stress disorder.
Carbamazepine derivatives with P2X4 receptor-blocking activity
Tian, Maoqun,Abdelrahman, Aliaa,Weinhausen, Stephanie,Hinz, Sonja,Weyer, Stefanie,Dosa, Stefan,El-Tayeb, Ali,Müller, Christa E.
supporting information, p. 1077 - 1088 (2014/02/14)
Antagonists for the P2 receptor subtype P2X4, an ATP-activated cation channel receptor, have potential as novel drugs for the treatment of neuropathic pain and other inflammatory diseases In the present study, a series of 47 carbamazepine derivatives including 32 novel compounds were designed, synthesized, and evaluated as P2X4 receptor antagonists Their potency to inhibit ATP-induced calcium influx in 1321N1 astrocytoma cells stably transfected with the human P2X4 receptor was determined Additionally, species selectivity (human, rat, mouse) and receptor subtype selectivity (P2X4 vs P2X1, 2, 3, 7) were investigated for selected derivatives The most potent compound of the present series, which exhibited an allosteric mechanism of P2X4 inhibition, was N,N-diisopropyl-5H-dibenz[b,f]azepine-5-carboxamide (34, IC50 of 3.44 μM) The present study extends the so far very limited knowledge on structure-activity relationships of P2X4 receptor antagonists
COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL DISORDERS
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Paragraph 00100; 00101, (2013/12/03)
The invention relates to the compounds of formula (I) and formula (1A) or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula (I) and formula (IA); and methods for treating or preventing neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment, of epilepsy, bipolar disorder, trigeminal neuralgia, attention-deficit, hyperactivity disorder (ADHD), schizophrenia, neuropathic pain, seizures, bipolar disorder, mania, phantom limb syndrome, complex regional pain syndrome, paroxysmal extreme pain disorder, neuromyotonia, intermittent explosive disorder, borderline personality disorder. Myotonia congenita and post-traumatic stress disorder.
