Quantum chemical calculations have been carried out to investigate the vibrational frequencies of clonazepam. The FTIR spectrum of clonazepam was recorded in the region 4000 to 400 cm–1 in the solid phase. The optimi...Quantum chemical calculations have been carried out to investigate the vibrational frequencies of clonazepam. The FTIR spectrum of clonazepam was recorded in the region 4000 to 400 cm–1 in the solid phase. The optimized geometry, wave number and intensity of the vibrational bands of clonazepam were obtained by ab initio Restricted Hartree Fock (RHF) and Density Functional Theory (DFT) methods with complete relaxation in the potential energy surface using the 6-31G (d,p) basis set. A complete vibrational assignment aided by the theoretical harmonic frequency analysis is proposed. The observed and the calculated wavenumbers are found to be in good agreement. The experimental spectra also coincide satisfactorily with those of theoretical spectra. Theoretical spectrograms for the IR spectrum were also constructed in RHF and B3LYP levels. In addition to this the RHF and DFT based NMR calculation procedure was used to assign the 1H NMR chemical shift of clonazepam. Theoretical values are compared with the experimental data.展开更多
Background： Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers （MERRFs） has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted ...Background： Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers （MERRFs） has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted to find more suitable treatments for it. In this study, the antimyoclonic effects ofmonotherapies, including levetiracetam （LEV）, clonazepam （CZP）, valproic acid （VPA）, and topiramate （TPM） compared to combination therapy group with LEV and CZP on MERRF, were evaluated to find a more advantageous approach on the treatment of myoclonic seizures. Methods： Treatments of myoclonic seizures with VPA, LEV, CZP, and TPM were reported as monotherapies in 17 MERRF patients from Qilu Hospital between 2003 and 2016, who were diagnosed through clinical data and genetic testing. After 1-4 months oflbllow-up （mean： 82.9 ± 28.1 days）, 12 patients that exhibited poor responses to monotherapy were given a combined treatment consisting of LEV and CZP subsequently. The lbllow-up period was 4-144 months （mean： 66.3 ± 45.3 months）, the effective rates of monotherapy group （17 patients） and combination therapy group （12 patients） were analyzed by Chi-square test. Results： The m.8344 A〉G mutation was detected in all patients. There were lbur patients with partial response （4/17, two in the CZP group and two in the LEV group）, ten patients with stable disease （10/17, six in the CZP group, three in the LEV group, and one in the TPM group）, and three patients with progressive disease （3/18, two in the VPA group and one in the TPM group）. Twelve of the patients with LEV combined with CZP showed a positive effect and good tolerance （12/12）, eight of them demonstrated improved cognition and coordination. There was a significant difference between the monotherapy group and combination therapy gToup in the efficacy ofantimyoclonic seizures （χ^2 = 13.7, P 〈 0.001 ）. Conclusions： LEV in combination with CZP is an efficient and sale treatment for myoclonic seizures in patients with this disease exhibiting the m.8344A〉G mutation.展开更多
Drug-facilitated sexual assault(DFSA)is a sexual act in which the victim is unable to give or rescind consent due to alcohol or drug intoxication,which involved the abuse of benzodiazepines around the world.Convention...Drug-facilitated sexual assault(DFSA)is a sexual act in which the victim is unable to give or rescind consent due to alcohol or drug intoxication,which involved the abuse of benzodiazepines around the world.Conventional techniques used for the analysis of benzodiazepines have the limitation of short detection time window due to the rapid metabolism of these drugs in body.This study aimed to investigate the characteristic changes of metabolites in the blood of rats after ingesting diazepam/clonazepam through a gas chromatography-mass spectrometry-based metabolomics method,allowing the indirect reveal of the rats ingested diazepam/clonazepam.First,we found that diazepam and clonazepam in the blood of rats could not be detected by liquid chromatography-tandem mass spectrometry after 48 h of ingestion.Then,orthogonal partial least squares discrimination analysis regression models were,respectively,constructed to determine whether the rats ingested diazepam/clonazepam after 48 h.The results showed that 5 metabolites were found to be associated with diazepam exposure,and 7 metabolites were found to be associated with clonazepam exposure,which may be characterization for the evaluation of digestion of diazepam and clonazepam in rat.展开更多
文摘Quantum chemical calculations have been carried out to investigate the vibrational frequencies of clonazepam. The FTIR spectrum of clonazepam was recorded in the region 4000 to 400 cm–1 in the solid phase. The optimized geometry, wave number and intensity of the vibrational bands of clonazepam were obtained by ab initio Restricted Hartree Fock (RHF) and Density Functional Theory (DFT) methods with complete relaxation in the potential energy surface using the 6-31G (d,p) basis set. A complete vibrational assignment aided by the theoretical harmonic frequency analysis is proposed. The observed and the calculated wavenumbers are found to be in good agreement. The experimental spectra also coincide satisfactorily with those of theoretical spectra. Theoretical spectrograms for the IR spectrum were also constructed in RHF and B3LYP levels. In addition to this the RHF and DFT based NMR calculation procedure was used to assign the 1H NMR chemical shift of clonazepam. Theoretical values are compared with the experimental data.
基金This study wassupported partly by grants from the National Natural Science Foundation of China （No. 81873786）, Programs for Science and Technology Development of Jinan （No. 201704102）, Lateral Chimerism Project of Shandong University （No. 12671731）, and the Programs for Science and Technology Development of Binzhou （No. 2014ZC0136）.
文摘Background： Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers （MERRFs） has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted to find more suitable treatments for it. In this study, the antimyoclonic effects ofmonotherapies, including levetiracetam （LEV）, clonazepam （CZP）, valproic acid （VPA）, and topiramate （TPM） compared to combination therapy group with LEV and CZP on MERRF, were evaluated to find a more advantageous approach on the treatment of myoclonic seizures. Methods： Treatments of myoclonic seizures with VPA, LEV, CZP, and TPM were reported as monotherapies in 17 MERRF patients from Qilu Hospital between 2003 and 2016, who were diagnosed through clinical data and genetic testing. After 1-4 months oflbllow-up （mean： 82.9 ± 28.1 days）, 12 patients that exhibited poor responses to monotherapy were given a combined treatment consisting of LEV and CZP subsequently. The lbllow-up period was 4-144 months （mean： 66.3 ± 45.3 months）, the effective rates of monotherapy group （17 patients） and combination therapy group （12 patients） were analyzed by Chi-square test. Results： The m.8344 A〉G mutation was detected in all patients. There were lbur patients with partial response （4/17, two in the CZP group and two in the LEV group）, ten patients with stable disease （10/17, six in the CZP group, three in the LEV group, and one in the TPM group）, and three patients with progressive disease （3/18, two in the VPA group and one in the TPM group）. Twelve of the patients with LEV combined with CZP showed a positive effect and good tolerance （12/12）, eight of them demonstrated improved cognition and coordination. There was a significant difference between the monotherapy group and combination therapy gToup in the efficacy ofantimyoclonic seizures （χ^2 = 13.7, P 〈 0.001 ）. Conclusions： LEV in combination with CZP is an efficient and sale treatment for myoclonic seizures in patients with this disease exhibiting the m.8344A〉G mutation.
基金The study was financially supported by the Project of the National Natural Sciences Foundation of China(81373239)The Innovation and Business Starting-oriented training program of College Students in Sichuan Province(C2020113713).
文摘Drug-facilitated sexual assault(DFSA)is a sexual act in which the victim is unable to give or rescind consent due to alcohol or drug intoxication,which involved the abuse of benzodiazepines around the world.Conventional techniques used for the analysis of benzodiazepines have the limitation of short detection time window due to the rapid metabolism of these drugs in body.This study aimed to investigate the characteristic changes of metabolites in the blood of rats after ingesting diazepam/clonazepam through a gas chromatography-mass spectrometry-based metabolomics method,allowing the indirect reveal of the rats ingested diazepam/clonazepam.First,we found that diazepam and clonazepam in the blood of rats could not be detected by liquid chromatography-tandem mass spectrometry after 48 h of ingestion.Then,orthogonal partial least squares discrimination analysis regression models were,respectively,constructed to determine whether the rats ingested diazepam/clonazepam after 48 h.The results showed that 5 metabolites were found to be associated with diazepam exposure,and 7 metabolites were found to be associated with clonazepam exposure,which may be characterization for the evaluation of digestion of diazepam and clonazepam in rat.
