Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Cinarizina/uso terapêutico , Flunarizina/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Piperazinas/uso terapêutico , Terminologia como Assunto , Bloqueadores dos Canais de Cálcio/classificação , Cinarizina/classificação , Flunarizina/classificação , Humanos , Piperazinas/classificaçãoRESUMO
With the issuance of this final order, the Administrator of the Drug Enforcement Administration places the substance MT-45 (Systematic IUPAC Name: 1-cyclohexyl-4-(1,2-diphenylethyl)piperazine), including its salts, isomers, and salts of isomers into schedule I of the Controlled Substances Act. This scheduling action is pursuant to the Controlled Substances Act and is required in order for the United States to discharge its obligations under the Single Convention on Narcotic Drugs, 1961. This action imposes the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances on persons who handle (manufacture, distribute, import, export, engage in research or conduct instructional activities with, or possess), or propose to handle, MT-45.
Assuntos
Analgésicos Opioides/classificação , Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , Piperazinas/classificação , Humanos , Estados UnidosRESUMO
BACKGROUND: We recently conducted a comprehensive review of the psychiatric inclusion/exclusion criteria used in 170 placebo-controlled antidepressant efficacy trials (AETs) published during the past 20 years and found that the criteria of more recent studies were significantly more restrictive than prior studies. Vortioxetine is the most recently approved medication for the treatment of major depressive disorder (MDD). We compared the inclusion/exclusion criteria of the vortioxetine studies to the criteria used in other AETs, and discuss the broader issue of the generalizability of AETs and the implications this might have for the labeling of antidepressants receiving FDA approval. METHODS: We conducted a comprehensive literature review of placebo-controlled AETs published from January, 1995 through December, 2014. We identified 170 AETs published during this 20 year period and compared the inclusion/exclusion criteria used in the 12 studies of vortioxetine to those used in the nonvortioxetine studies. A second analysis compared vortioxetine to the 3 antidepressants most recently approved prior to vortioxetine (desvenlafaxine, levomilnacipran extended release, vilazodone). RESULTS: Compared to the nonvortioxetine AETs, the vortioxetine studies significantly more often excluded patients with any comorbid Axis I disorder (p<.001) and more often required the current depressive episode to be longer than the DSM minimum symptom duration requirement of 2 weeks (p<.01). The cutoff on the Montgomery Asberg Depression Rating Scale required for inclusion in the vortioxetine studies was higher than the cutoff used in the other AETs (p<.01). LIMITATIONS: A limitation of the present analysis is that it was based on published placebo-controlled studies of antidepressants. CONCLUSION: The inclusion/exclusion criteria in the studies of vortioxetine were more restrictive than the criteria used in other AETs. Inconsistent with FDA guidelines on the labeling of medications, the label of vortioxetine does not include a description of the limits to the group of patients with MDD for whom the medication has been shown to be effective.
Assuntos
Antidepressivos/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Transtorno Depressivo/tratamento farmacológico , Seleção de Pacientes , Piperazinas/uso terapêutico , Rotulagem de Produtos/estatística & dados numéricos , Sulfetos/uso terapêutico , Adulto , Antidepressivos/classificação , Feminino , Humanos , Masculino , Piperazinas/classificação , Escalas de Graduação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Sulfetos/classificação , VortioxetinaRESUMO
The present review is focused on the specific features of metabolism of designer drugs based on piperazine derivatives. Selected physicochemical properties of the key metabolites of these compounds are described with special reference to their effect on the behavior of these drugs in the human organism.. Recommendations on the analysis of the markers and methods of sample preparation for the identification of the main psychoactive piperazine derivatives are proposed.
Assuntos
Piperazinas , Drogas Desenhadas , Toxicologia Forense/métodos , Humanos , Piperazinas/classificação , Piperazinas/farmacocinética , Psicotrópicos/classificação , Psicotrópicos/farmacocinética , Detecção do Abuso de Substâncias/métodosAssuntos
Centros Médicos Acadêmicos/organização & administração , Distinções e Prêmios , Desenho de Fármacos , Descoberta de Drogas , Indústria Farmacêutica/organização & administração , Neoplasias/terapia , Benzamidas , Ensaios Clínicos como Assunto , História do Século XX , História do Século XXI , Humanos , Mesilato de Imatinib , Neoplasias/genética , Piperazinas/síntese química , Piperazinas/química , Piperazinas/classificação , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/classificação , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/síntese química , Pirimidinas/química , Pirimidinas/classificação , Pirimidinas/uso terapêutico , Estados UnidosRESUMO
The synthesis and SAR of a series of arylsulfonylpiperazine inhibitors of 11beta-HSD1 are described. Optimization rapidly led to potent, selective, and orally bioavailable inhibitors demonstrating efficacy in a cynomolgus monkey ex vivo enzyme inhibition model.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Ácidos Arilsulfônicos/síntese química , Piperazinas/síntese química , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Administração Oral , Animais , Ácidos Arilsulfônicos/classificação , Ácidos Arilsulfônicos/farmacologia , Disponibilidade Biológica , Linhagem Celular , Cristalografia por Raios X , Estabilidade Enzimática/efeitos dos fármacos , Estabilidade Enzimática/fisiologia , Humanos , Macaca fascicularis , Camundongos , Piperazinas/classificação , Piperazinas/farmacologia , Ratos , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: This article considers the process of re-classification of prescription drugs from prescription-only medications to over-the-counter (OTC) prescription drugs. SOURCES OF DATA: The recent change in classification for emergency contraception and simvastatin is explored in detail with similarities and differences being considered for a similar argument to be made for sildenafil. AREAS OF AGREEMENT: The benefits for patients, physicians and other healthcare professionals are considered in detail. AREAS OF CONTROVERSY: We raise concerns about recently developed and existing patient group directions that, although extensive in their assessment, may omit to identify significant contributory factors which would necessitate appropriate medical intervention. GROWING POINTS: While the decision for re-classification to OTC would depend on a number of factors, we argue that, with the proviso of proper assessments being made, sildenafil should be made available as an OTC medication. AREAS TIMELY FOR DEVELOPING RESEARCH: The safety and use of OTC medications for erectile dysfunction at a time when many first line prescription agents are reaching generic status.
Assuntos
Disfunção Erétil/tratamento farmacológico , Medicamentos sem Prescrição/provisão & distribuição , Inibidores de Fosfodiesterase/provisão & distribuição , Piperazinas/provisão & distribuição , Sulfonas/provisão & distribuição , Qualidade de Produtos para o Consumidor , Disfunção Erétil/psicologia , Feminino , Humanos , Masculino , Medicamentos sem Prescrição/classificação , Assistência Farmacêutica , Piperazinas/classificação , Guias de Prática Clínica como Assunto , Medicamentos sob Prescrição , Purinas/classificação , Purinas/provisão & distribuição , Citrato de Sildenafila , Sulfonas/classificaçãoRESUMO
The piperazinone derivatives have potential application in the pharmaceutical, polymer and textile fields. The present work describes the preparation of a series of new 1,4-diarylsubstituted-2-piperazinones by condensation of substituted N,N'-bis-(2-hydroxyphenyl)-ethylenediamines with glyoxal and the complete (13)C NMR spectral assignment accomplished using APT, HMQC and HMBC techniques. Substituent chemical-shift effects (SCS) were calculated, which showed different values for the lactam- and amine-substituted aromatic rings. The results show that predictions based on SCS effects are not simple for these molecules due to electronic and steric effects. Moreover, in the case of the ortho-substituted derivative 2 g, the NMR spectra reveal a dynamic behavior related to restricted rotation of the phenyl groups (atropisomerism).
Assuntos
Espectroscopia de Ressonância Magnética/métodos , Piperazinas/química , Piperazinas/síntese química , Isótopos de Carbono , Piperazinas/classificaçãoRESUMO
This report presents the recommendations of a WHO Expert Committee responsible for reviewing information on dependence-producing drugs to assess the need for their international control. The first part of the report contains a summary of the Committee's evaluations of seven substances (dronabinol, oripavine, buprenorphine, butorphanol, ketamine, khat and zopiclone). The report also discusses the substances that were pre-reviewed (gamma-hydroxybutyric acid and tramadol) and recommended gamma-hydroxybutyric acid for critical review at a future meeting. Two substances (gamma-butyrolactone and 1,4-butanediol) were identified for future pre-review). The second part of the report discusses the guidelines for the WHO review of dependence-producing psychoactive substances for international control. It includes sections on amending the current guidelines, interpretation of specific aspects of the guidelines and access to information necessary for the evaluation of substances. The final section considers other matters including activities of the EMCCDA, the use of pharmacovigilance data, promotion of education and information on the appropriate use of psychoactive drugs and the impact of international control on medical availability of substances.
Assuntos
Avaliação de Medicamentos , Controle de Medicamentos e Entorpecentes , Acessibilidade aos Serviços de Saúde/normas , Psicotrópicos/classificação , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , 4-Butirolactona/classificação , Comitês Consultivos , Compostos Azabicíclicos , Buprenorfina/classificação , Butorfanol/classificação , Catha/classificação , Dronabinol/classificação , Humanos , Hidroxibutiratos/classificação , Ketamina/classificação , Piperazinas/classificação , Psicotrópicos/farmacologia , Psicotrópicos/uso terapêutico , Tebaína/análogos & derivados , Tebaína/classificação , Tramadol/classificação , Organização Mundial da SaúdeRESUMO
A novel diketopiperazine, named cyclo-(D-pipecolinyl-L-isoleucine) (DKP 1), and 7 known diketopiperazines were isolated from the cell-free culture supernatant of the Antarctic psychrophilic bacterium Pseudoalteromonas haloplanktis TAC125. Two diketopiperazines containing pipecolinyl moiety were isolated for the first time from a natural source. Two new linear peptides, stable to bacterial proteolytic enzymes, were also characterized. The structures of the isolated compounds were elucidated by means of spectroscopic data (1D-, 2D-NMR, EIMS, FABMS, and ESIMS/MS) and chiral high-performance liquid chromatography. The potential antioxidant activity of the isolated compounds was evaluated by a DPPH free radical scavenging assay.
Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/classificação , Piperazinas/química , Pseudoalteromonas/química , Pseudoalteromonas/metabolismo , Sequência de Aminoácidos , Regiões Antárticas , Antioxidantes/análise , Proteínas de Bactérias/isolamento & purificação , Dicetopiperazinas , Dimetil Sulfóxido , Fermentação , Espectroscopia de Ressonância Magnética/métodos , Conformação Molecular , Piperazinas/classificação , Piperazinas/isolamento & purificação , Pseudoalteromonas/crescimento & desenvolvimento , Pseudoalteromonas/isolamento & purificaçãoRESUMO
With the issuance of this final rule, the Deputy Administrator of the Drug Enforcement Administration (DEA) places the substance, zopiclone, including its salts, isomers and salts of isomers into Schedule IV of the Controlled Substances Act (CSA). As a result of this rule, the regulatory controls and criminal sanctions of Schedule IV will be applicable to the manufacture, distribution, dispensing, importation and exportation of zopiclone and products containing zopiclone.
Assuntos
Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , Piperazinas/classificação , Depressores do Sistema Nervoso Central/classificação , Humanos , Legislação de Medicamentos , Estados Unidos , United States Food and Drug AdministrationAssuntos
Antipsicóticos/uso terapêutico , Tratamento de Emergência/métodos , Piperazinas/uso terapêutico , Agitação Psicomotora/tratamento farmacológico , Tiazóis/uso terapêutico , Antipsicóticos/classificação , Droperidol/efeitos adversos , Rotulagem de Medicamentos , Tratamento de Emergência/normas , Humanos , Síndrome do QT Longo/induzido quimicamente , Piperazinas/classificação , Guias de Prática Clínica como Assunto , Tiazóis/classificação , Torsades de Pointes/induzido quimicamente , Estados Unidos , United States Food and Drug AdministrationRESUMO
This final rulemaking is issued by the Acting Deputy Administrator of the Drug Enforcement Administration (DEA) to place 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7) and N-benzylpiperazine (BZP) into Schedule I of the Controlled Substances Act (CSA). This action by the DEA Acting Deputy Administrator is based on a scheduling recommendation by the Department of Health and Human Services (DHHS) and a DEA review indicating that 2C-T-7 and BZP meet the criteria for placement in Schedule I of the CSA. This final rule will continue to impose the regulatory controls and criminal sanctions of Schedule I substances on the manufacture, distribution, and possession of 2C-T-7 and BZP.
Assuntos
Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , Fenetilaminas/classificação , Piperazinas/classificação , Anfetaminas/efeitos adversos , Rotulagem de Medicamentos , Humanos , Legislação de Medicamentos , Fenetilaminas/efeitos adversos , Fenetilaminas/análise , Piperazinas/efeitos adversos , Piperazinas/análise , Saúde Pública , Transtornos Relacionados ao Uso de Substâncias , Estados Unidos , United States Dept. of Health and Human Services , United States Food and Drug AdministrationRESUMO
Urapidil is a new antihypertensive vasodilator agent whose pharmacologic action in man has not yet been fully defined. We have assessed the alpha adrenergic blocking activity of urapidil 15 and 30 mg given intravenously in a single blind study in 8 healthy volunteers. Urapidil produced dose-dependent parallel shift of the phenylephrine log dose/blood pressure response curve, consistent with significant competitive peripheral alpha 1 antagonism. Mean dose ratios were 2.99 and 5.48 for the 15 mg and 30 mg doses respectively. The pA2 for alpha 1 blockade is 7.3. Given these data, the major mechanism of antihypertensive effect of urapidil may be alpha 1 antagonism in the peripheral vasculature.