Search results for "Azepine"

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Carbamazepine.

2020

Abstract Literature relevant to assessing whether BCS-based biowaivers can be applied to immediate release (IR) solid oral dosage forms containing carbamazepine as the single active pharmaceutical ingredient are reviewed. Carbamazepine, which is used for the prophylactic therapy of epilepsy, is a non-ionizable drug that cannot be considered “highly soluble” across the range of pH values usually encountered in the upper gastrointestinal tract. Furthermore, evidence in the open literature suggests that carbamazepine is a BCS Class 2 drug. Nevertheless, the oral absolute bioavailability of carbamazepine lies between 70 and 78% and both in vivo and in vitro data support the classification of ca…

Carbamazepine exposure in the sea anemones Anemonia sulcata and Actinia equina: Metabolite identification and physiological responses

2020

Trabajo presentado en el 11º Congreso Ibérico, 8º Iberoamericano de Contaminación y Toxicología (CICTA 2018) celebrado en la Escuela Técnica Superior de Ingeniería de Montes, Forestal y del Medio Natural, Madrid del 11 al 13 de julio de 2018

Effects of the benzodiazepine receptor agonist midazolam and antagonist flumazenil on 5-hydroxytryptamine release from guinea-pig intestine in vitro

1990

Isolated segments of the guinea-pig small intestine and the guinea-pig stomach were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid into the portal venous effluent determined by high pressure liquid chromatography with electrochemical detection. Test substances were applied intraarterially. The benzodiazepine receptor agonist, midazolam, concentration-dependently increased (by 58%, at 1 nmol/l) and decreased (by 32%, at 100 nmol/l) the release of 5-HT from small intestine preparations. Both effects were blocked by the benzodiazepine receptor antagonist flumazenil (10 nmol/l) The stimulatory effect of midazolam was also abolished in the presen…

[ 18 F]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors

2001

5-(2'-[18F]Fluoroethyl)flumazenil ([18F]FEF) is a fluorine-18 labelled positron emission tomography (PET) tracer for central benzodiazepine receptors. Compared with the established [11C]flumazenil, it has the advantage of the longer half-life of the fluorine-18 label. After optimisation of its synthesis and determination of its in vitro receptor affinities, we performed first PET studies in humans. PET studies in seven healthy human volunteers were performed on a Siemens ECAT EXACT whole-body scanner after injection of 100-280 MBq [L8F]FEF. In two subjects, a second PET scan was conducted after pretreatment with unlabelled flumazenil (1 mg or 2.5 mg i.v., 3 min before tracer injection). A t…

Benzodiazepines for catatonic symptoms, stupor, and mutism.

1988

Comparative study of the toxicity of molinate for freshwater organisms.

2003

The GABAergic effect of low doses of lorazepam on social behavior

2002

The aim of this work was to test the antiaggressive effects of lorazepam and to determine whether these effects were mediated by benzodiazepine receptors. In a first experiment, male mice were injected with lorazepam in a range of low doses (0.05, 0.1, 0.2, and 0.6 mg/kg) or saline solution. In a second experiment, 1 mg/kg of Ro 15-1788, a benzodiazepine receptor antagonist, and a saline solution were injected before the behavioral test. Results showed that 0.6 mg/kg of lorazepam was the only dose that decreased the total duration of threat ( P < .01) and social investigation ( P < .05) and that 1 mg/kg of Ro 15-1788 had no effects. In the third experiment, animals received two injec- tions…

Benzodiazepine receptor interactions may be involved in the neurotoxicity of various penicillin derivatives

1980

The interaction of seven penicillin derivatives with specific [3H]flunitrazepam binding to benzodiazepine receptors was investigated. The affinities of the penicillins for benzodiazepine receptor seemed to depend on the lipophilia of the derivatives. The concentrations of the penicillins which inhibit specific [3H]flunitrazepam binding are consistent with penicillin levels found in the central nervous system of patients developing penicillin induced convulsions. The results suggest that penicillins inhibit GABAergic transmission not only at the GABA receptor, but also at the benzodiazepine receptor, which is thought to be part of a neuronal system facilitating GABAergic transmission. Both m…

The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes.

1998

The amino acid gamma-aminobutyric-acid (GABA) prevails in the CNS as an inhibitory neurotransmitter that mediates most of its effects through fast GABA-gated Cl(-)-channels (GABAAR). Molecular biology uncovered the complex subunit architecture of this receptor channel, in which a pentameric assembly derived from five of at least 17 mammalian subunits, grouped in the six classes alpha, beta, gamma, delta, sigma and epsilon, permits a vast number of putative receptor isoforms. The subunit composition of a particular receptor determines the specific effects of allosterical modulators of the GABAARs like benzodiazepines (BZs), barbiturates, steroids, some convulsants, polyvalent cations, and et…

Synthesis and induction of G0–G1 phase arrest with apoptosis of 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazep…

2007

The multistep synthesis of 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one 15 has been carried out. The compound showed antiproliferative and apoptotic effects against K562, K562-R (imatinib mesilate resistant), HL60 and multidrug resistant (MDR) HL60 cell lines. Compound 15 showed a pro-apoptotic activity against HL60 and K562 resistant cell lines markedly higher than etoposide and busulfan, respectively. Flow cytometry studies carried out on K562 cells allowed to establish that 15 induces G0-G1 phase arrest followed by apoptosis.