vardenafil-dihydrochloride and Chronic-Disease

The aim of this study was to evaluate the safety and efficacy of vardenafil in outpatients with chronic schizophrenia and erectile dysfunction and to investigate any effect on quality of life in this population.. In this 12-week, open-label, flexible-dose study, 25 outpatients with chronic schizophrenia (DSM-IV criteria) and erectile dysfunction received vardenafil 10 mg as needed (at a maximum of 1 dose per day) with the option to maintain current dose or to titrate to 5 mg or 20 mg at 4 and 8 weeks. Assessment was performed with the International Index of Erectile Function (IIEF) at base line and at weeks 4, 8, and 12. The Quality of Life Scale (QLS) was administered at baseline and at week 12. The study was carried out at the Psychiatric Hospital of Athens, Greece, between October 2005 and November 2006.. Vardenafil produced a statistically significant improvement in all IIEF domains [erectile function (p < .001), orgasmic function (p < .05), sexual desire (p < .05), intercourse satisfaction (p < .01), and overall satisfaction (p < .001)] and QLS (p < .003). Results were similar for the intention-to-treat (N = 25) and completer (N = 21, 84%) groups. Adverse events were infrequent and decreased in incidence over the course of the study.. Vardenafil was generally well tolerated and highly effective in outpatients with chronic schizophrenia and erectile dysfunction. The response to vardenafil was not influenced by certain patient characteristics, such as erectile dysfunction severity or serum prolactin levels. Improvement in sexual function was correlated with improvement in the quality of life.

Topics: Adult; Aged; Analysis of Variance; Chronic Disease; Drug Administration Schedule; Erectile Dysfunction; Greece; Humans; Imidazoles; Male; Middle Aged; Orgasm; Outpatients; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Prolactin; Prospective Studies; Quality of Life; Research Design; Schizophrenia; Sulfones; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Vardenafil has been found to be potent in pulmonary hypertension; however, the underlying mechanisms remain poorly understood. To address this issue, we investigated the underlying mechanisms of vardenafil in the contribution of Ca(2+) signaling and mobilization in modifying vasoconstriction of pulmonary arteries in hypoxic mice.. Hemodynamic measurements and morphological studies were performed. Muscle tension was measured by PowerLab system. I(Ca,L) was recorded using a perforated patch-clamp technique. [Ca(2+)](i) was measured using a fluorescence imaging system.. Vardenafil greatly inhibited RVSP increases, RV hypertrophy and ameliorated pulmonary artery remodeling in response to chronic hypoxia. Membrane depolarization following 50 mM high K(+)-caused muscle contraction significantly decreased from 101.7 ± 10.1 in the hypoxia group to 81.8 ± 5.0 mg in hypoxia plus vardenafil arteries. Fifty mM high K(+)-elicited increase [Ca(2+)](i) was markedly decreased from 610.6 ± 71.8 in hypoxia cells to 400.3 ± 47.2 nM in hypoxia plus vardenafil cells. Application of vardenafil greatly inhibited the density of I(Ca,L) by 37.7% compared with that in the hypoxia group. Administration of 1 μM phenylephrine to stimulate α(1)-adrenergic receptor resulted in a smaller increase in [Ca(2+)](i) in hypoxia plus vardenafil cells than that in hypoxia cells. One hundred μM ATP-mediated increase in [Ca(2+)](i) was also inhibited in vardenafil-hypoxia group (from 625.8 ± 62.3 to 390.9 ± 38.1 nM), suggesting that internal calcium reserves contribute to neurotransmitter-induced Ca(2+) release from the SR through IP(3)Rs in PASMCs.. Vardenafil may effectively block Ca(2+) influx through L-type Ca(2+) channel and inhibit the Ca(2+) release from SR through IP(3)Rs, thus enhancing its vasorelaxation of pulmonary arteries under hypoxia conditions.

Topics: Adenosine Triphosphate; Adrenergic alpha-Agonists; Animals; Calcium; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Signaling; Chronic Disease; Drug Evaluation, Preclinical; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Imidazoles; Inositol 1,4,5-Trisphosphate Receptors; Ion Transport; Male; Mice; Mice, Inbred C57BL; Myocytes, Smooth Muscle; Patch-Clamp Techniques; Phenylephrine; Piperazines; Potassium; Sarcoplasmic Reticulum; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilation; Vasodilator Agents