Search results for "Benzazepines"
showing 10 items of 38 documents
Altered gastrointestinal motility in an animal model of Lesch-Nyhan disease.
2018
Mutations in the HGPRT1 gene, which encodes hypoxanthine-guanine phosphoribosyltransferase (HGprt), housekeeping enzyme responsible for recycling purines, lead to Lesch-Nyhan disease (LND). Clinical expression of LND indicates that HGprt deficiency has adverse effects on gastrointestinal motility. Therefore, we aimed to evaluate intestinal motility in HGprt knockout mice (HGprt(−)). Spontaneous and neurally evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips of distal colon. HGprt(−) tissues showed a lower in amplitude spontaneous activity and atropine-sensitivity neural contraction compared to control mice. The responses to carbachol a…
Lorcaserin bidirectionally regulates dopaminergic function site-dependently and disrupts dopamine brain area correlations in rats
2020
Abstract Lorcaserin, which is a selective agonist of serotonin2C receptors (5-HT2CRs), is a new FDA-approved anti-obesity drug that has also shown therapeutic promise in other brain disorders, such as addiction and epilepsy. The modulation of dopaminergic function might be critical in the therapeutic effect of lorcaserin, but its exact effect is unknown. Here, we studied the effect of the peripheral administration of lorcaserin on the ventral tegmental area (VTA), the substantia nigra pars compacta (SNc) dopaminergic neural activity, dopamine (DA) dialysis levels in the nucleus accumbens and striatum and on DA tissue levels in 29 different rat brain regions. Lorcaserin (5–640 μg/kg, i.v.) m…
Developmental effects of the protein kinase inhibitor kenpaullone on the sea urchin embryo
2017
The selection and validation of bioactive compounds require multiple approaches, including in-depth analyses of their biological activity in a whole-animal context. We exploited the sea urchin embryo in a rapid, medium-scale range screening to test the effects of the small synthetic kinase inhibitor kenpaullone. We show that sea urchin embryos specifically respond to this molecule depending on both dose and timing of administration. Phenotypic effects of kenpaullone are not immediately visible, since this molecule affects neither the fertilization nor the spatial arrangement of blastomeres at early developmental stages. Nevertheless, kenpaullone exposure from the beginning of embryogenesis …
Effectiveness of eslicarbazepine acetate in dependency of baseline anticonvulsant therapy: Results from a German prospective multicenter clinical pra…
2019
Abstract Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved as monotherapy for partial-onset seizures in adults and as adjunctive therapy in patients aged above 6 years in the European Union (EU). The prospective observational Zebinix Effects in DEpendency of BAseline Conditions (ZEDEBAC) study aimed at investigating the effectiveness of ESL in clinical practice, with ESL being administered as monotherapy (mono group), as only add-on to a current monotherapy (1 + group), or as add-on to ≥ 2 baseline AEDs (≥ 2 + group). In total, 237 patients were included, 35 in the mono group, 114 in the 1 +, and 88 in the ≥ 2 + group. Six-month retention rates were 93.9%…
Examination and treatment of sleep-related painful erections--a case report.
1989
The case of a patient with sleep-related painful erections is described. Insomnia and a slight depressive syndrome occurred along with a long history of this disorder. No physical abnormality was found. At a baseline recording of sleep electroencephalography (EEG) and nocturnal penile tumescence (NPT), a disturbed sleep pattern and impaired NPT were recorded. Attempts to treat the disorder with diazepam, amitriptyline, trimipramine, and biperidene did not prompt a stable improvement of the disorder, but a dosage of 25 mg clozapine was sufficient to achieve normalized sleep architecture, remission of the depressive symptomatology, and normalization of NPT. It is likely that marked sedation i…
Nemaline myopathy and heart failure: role of ivabradine; a case report
2015
Background Nemaline myopathy (NM) is a rare congenital myopathy characterized by muscle weakness, hypotonia and the presence in muscle fibers of inclusions known as nemaline bodies and a wide spectrum of clinical phenotypes, ranging from severe forms with neonatal onset to asymptomatic forms. The adult-onset form is heterogeneous in terms of clinical presentation and disease progression. Cardiac involvement occurs in the minority of cases and little is known about medical management in this subgroup of NM patients. We report a rare case of heart failure (HF) in a patient with adult-onset NM in whom ivabradine proved to be able to dramatically improve the clinical picture. Case presentation …
Menopause and ovariectomy cause a low grade of systemic inflammation that may be prevented by chronic treatment with low doses of estrogen or losarta…
2009
Abstract The incidence of cardiovascular diseases in premenopausal women is lower than in men or postmenopausal women. This study reports the discovery of a low grade of systemic inflammation, including monocyte adhesion to arterial endothelium, elicited by menopause or estrogen depletion. Chronic treatment with low dose of 17-β-estradiol or inhibition of the renin-angiotensin system reduced this inflammation. Using an in vitro flow chamber system with human arterial and venous endothelial cells, we found that leukocytes from healthy postmenopausal women were more adhesive to the arterial endothelium than those from premenopausal women regardless of the stimulus used on endothelial cells. I…
Modulation by fenoldopam (SKF 82526) and bromocriptine of the electrically evoked release of vasopressin from the rat neurohypophysis. Effects of dop…
1986
1. Single neurointermediate lobes were fixed by their stalks to a platinum wire electrode and incubated in Krebs-bicarbonate solution. Vasopressin release into the medium was determined by a radioimmunoassay. Vasopressin secretion was increased by electrical stimulation (15 Hz, 10 s trains with 10 s intervals for 10 min). 2. Fenoldopam (SKF 82526) had a dual effect on vasopressin release, 30 nM decreasing (by 30%) and 3 μM increasing (by 32%) the evoked vasopressin secretion. The facilitatory effect of fenoldopam was antagonized in a concentration-dependent manner by flupenthixol but not by sulpiride. Sulpiride (1 μM) prevented the inhibitory effect of fenoldopam (30 μM). 3. After pretreatm…
Phase I Assessment of New Mechanism-Based Pharmacodynamic Biomarkers for MLN8054, a Small-Molecule Inhibitor of Aurora A Kinase
2011
Abstract The mitotic kinase Aurora A is an important therapeutic target for cancer therapy. This study evaluated new mechanism-based pharmacodynamic biomarkers in cancer patients in two phase I studies of MLN8054, a small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received MLN8054 orally for 7 consecutive days in escalating dose cohorts, with skin and tumor biopsies obtained before and after dosing. Skin biopsies were evaluated for increased mitotic cells within the basal epithelium. Tumor biopsies were assessed for accumulation of mitotic cells within proliferative tumor regions. Several patients in the highest dose cohorts showed marked increases in the ski…
The lack of the effect of DA-1 and DA-2 dopamine agonists on the isolated guinea-pig atria.
1987
1 The effects of dopamine and both DA-1 and DA-2 dopamine receptor agonists have been studied on the contractile force of electrically driven guinea-pig left atria and frequency of spontaneously beating right atria. 2 Pretreatment of animals with reserpine caused a parallel rightward shift of the concentration-response curve to dopamine of either preparation. 3 Propranolol, but not domperidone, shifted to the right the dose-response curve for the positive inotropic and chronotropic effects of dopamine. 4 Neither apomorphine, fenoldopam, bromocriptine nor piribedil had effects on the frequency and contractile force of the isolated guinea-pig atria. 5 These results suggest that DA-1 and DA-2 …