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Phosphodiesterase Inhibitor

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6621. Amrinone, a phosphodiesterase III inhibitor, and arachidonic acid metabolism in humans. (Abstract)

Amrinone, a phosphodiesterase III inhibitor, and arachidonic acid metabolism in humans. Amrinone-a phosphodiesterase III inhibitor-is used in the treatment of acute heart failure. In addition to its hemodynamic effects, amrinone has been shown to inhibit thromboxane synthesis in vitro. We investigated the effects of amrinone on thromboxane, prostaglandin, and leukotriene synthesis in humans. Eight healthy male volunteers took part in this single-blind study in which either amrinone (a 1.5-mg/kg

1999 Journal of cardiovascular pharmacology

6622. Acute hemodynamic effects and preload-dependent cardiovascular profile of the partial phosphodiesterase inhibitor nanterinone in patients with mild to moderate heart failure. (Abstract)

Acute hemodynamic effects and preload-dependent cardiovascular profile of the partial phosphodiesterase inhibitor nanterinone in patients with mild to moderate heart failure. Nanterinone (UK-61,260) is a novel positive inotropic and balanced-type vasodilating drug, only partially based on phosphodiesterase III inhibition. Preliminary data from controlled studies suggest satisfactory long-term efficacy and safety. As its acute hemodynamic effects in humans are unknown, an oral dose of 2 mg (...) nanterinone was studied in 14 patients with heart failure (NYHA class II-III) on chronic diuretic and angiotensin-converting enzyme (ACE) inhibitor treatment. Before the study, patients were on a 2 g salt-balanced diet, and they received their last medication 16 hours before each study day. Hemodynamic measurements were carried out before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours after administration of the study drug. All patients received placebo and nanterinone on 2 consecutive days. Following

1996 Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy

6623. Therapeutic use of a selective cAMP phosphodiesterase inhibitor (Rolipram) in Parkinson's disease. (Abstract)

Therapeutic use of a selective cAMP phosphodiesterase inhibitor (Rolipram) in Parkinson's disease. The effects of Rolipram, a new phosphodiesterase inhibitor, were assessed in a double-blind trial versus placebo in 10 patients with Parkinson's disease already under treatment. Contrary to previous findings with specific phosphodiesterase inhibitors, with Rolipram (at the dose of 3 mg per day), no significant deterioration of the therapeutic action of dopamine agonist Lisuride was noted.

1983 Pharmacological research communications

6624. Bronchodilatory effect of inhaled zardaverine, a phosphodiesterase III and IV inhibitor, in patients with asthma. (Abstract)

Bronchodilatory effect of inhaled zardaverine, a phosphodiesterase III and IV inhibitor, in patients with asthma. Zardaverine is a newly developed selective phosphodiesterase III and IV inhibitor. This study investigates the bronchodilatory properties of zardaverine, administered by inhalation. Twelve patients with reversible bronchial obstruction (increase in forced expiratory volume in one second (change FEV1 % predicted) at least 15% after 200 micrograms salbutamol, median age 31 yrs, range

1992 The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology

6625. Plasma factor and platelet sensitivity to prostacyclin in patients with peripheral vascular disease before and after treatment with a combination of a cyclooxygenase and a phosphodiesterase inhibitor. (Abstract)

Plasma factor and platelet sensitivity to prostacyclin in patients with peripheral vascular disease before and after treatment with a combination of a cyclooxygenase and a phosphodiesterase inhibitor. According to a pathogenetic concept originally presented by Moncada in 1977 a therapeutic combination of a low-dose cyclooxygenase inhibitor with a phosphodiesterase inhibitor might help in restoring a disturbed hemostatic balance, as thromboxane synthesis in the platelets should be inhibited (...) to a greater extent than the prostacyclin synthesis of the endothelium. Therefore, we evaluated the influence of a therapeutic combination of cyclooxygenase inhibitors in different dosages (sulfinpyrazone, acetylsalicylic acid) with a phosphodiesterase inhibitor (dipyridamole) on platelet sensitivity and plasma factor in comparison to placebo treatment. We examined 76 males with peripheral vascular disease (PVD) stage IIa according to Fontaine in a double-blind randomized study over a 3 months period

1984 Prostaglandins, leukotrienes, and medicine Controlled trial quality: uncertain

6626. Effect of selective phosphodiesterase 3 inhibition on the early and late asthmatic responses to inhaled allergen. Full Text available with Trip Pro

Effect of selective phosphodiesterase 3 inhibition on the early and late asthmatic responses to inhaled allergen. Phosphodiesterase isoenzymes may play an important role in the regulation of airway calibre and bronchial smooth muscle function. Immunomodulatory actions may also be important in allergic airway inflammation. We have examined the effect of a phosphodiesterase (PDE) 3 inhibitor (MKS492) on the early and late responses to inhaled allergen in 18 atopic asthmatic subjects.On three (...) mg group. Late phase responses as assessed by 4 h % post-saline FEV1 was significantly improved by MKS 492 40 mg to 90.0% (6.3) vs 83.0% (12.4) for placebo-difference 7.0, 95% CI (0.1, 13.9), but again not by the 20 mg dose. Analysis of the area under the FEV1 response-time course curves showed non-significant reduction in the late response after the 40 mg dose (placebo 159.0, 134.8) vs 128.1, [81.5] for 40 mg).A novel PDE 3 inhibitor significantly decreases the early bronchoconstrictor response

1998 British journal of clinical pharmacology Controlled trial quality: uncertain

6627. Does phosphodiesterase III inhibition reverse the cardiodepressive effects of propofol? (Abstract)

Does phosphodiesterase III inhibition reverse the cardiodepressive effects of propofol? Propofol decreases arterial blood pressure as a result of reduced cardiac output and peripheral vasodilation, raising concerns about its safety in patients with impaired cardiovascular function. Phosphodiesterase III inhibitors (PDE-III-Inh) have gained attention as inotropic drugs. We therefore studied whether the cardiac effects of propofol could be abrogated by enoximone. Twenty-one patients

1997 Anesthesia and analgesia Controlled trial quality: uncertain

6628. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. (Abstract)

Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Sildenafil (Viagra, UK-92,480) is a novel oral agent under development for the treatment of penile erectile dysfunction. Erection is dependent on nitric oxide and its second messenger, cyclic guanosine monophosphate (cGMP). However, the relative importance of phosphodiesterase (PDE) isozymes is not clear. We have identified both cGMP- and cyclic adenosine (...) monophosphate-specific phosphodiesterases (PDEs) in human corpora cavernosa in vitro. The main PDE activity in this tissue was due to PDE5, with PDE2 and 3 also identified. Sildenafil is a selective inhibitor of PDE5 with a mean IC50 of 0.0039 microM. In human volunteers, we have shown sildenafil to have suitable pharmacokinetic and pharmacodynamic properties (rapid absorption, relatively short half-life, no significant effect on heart rate and blood pressure) for an oral agent to be taken, as required

1996 International journal of impotence research Controlled trial quality: uncertain

6629. Is phosphodiesterase inhibition a new mechanism of antidepressant action? A double blind double-dummy study between rolipram and desipramine in hospitalized major and/or endogenous depressives. (Abstract)

Is phosphodiesterase inhibition a new mechanism of antidepressant action? A double blind double-dummy study between rolipram and desipramine in hospitalized major and/or endogenous depressives. Unlike conventional antidepressants, rolipram (a new approach in the treatment of depression) stimulates both the presynaptic and the postsynaptic component of monoaminergic transmission. Several double blind trials are under way to assess the clinical efficacy and safety of this compound. The present

1988 European archives of psychiatry and neurological sciences Controlled trial quality: uncertain

6630. [Enoximone, a new phosphodiesterase inhibitor: the spectrum of applications during heart surgery--a comparison with dobutamine]. (Abstract)

[Enoximone, a new phosphodiesterase inhibitor: the spectrum of applications during heart surgery--a comparison with dobutamine]. During cardiac surgery treatment of deterioration of myocardial function is usually based on catecholamines. Development of selective phosphodiesterase-(PDE-)III-inhibitors seems to be a new aspect in treating myocardial dysfunction. Therefore the hemodynamic effects of the new PDE-inhibitor enoximone were investigated in 20 coronary surgery patients unable

1988 Herz Controlled trial quality: uncertain

6631. Controlled and uncontrolled studies of phosphodiesterase III inhibitors in contemporary cardiovascular medicine. (Abstract)

Controlled and uncontrolled studies of phosphodiesterase III inhibitors in contemporary cardiovascular medicine. The phosphodiesterase inhibitors are new inotrope vasodilators that have beneficial hemodynamic effects in patients with congestive heart failure (CHF). The most extensively studied agents are milrinone and enoximone. Both drugs have clearly been shown in numerous studies to improve hemodynamics in patients with CHF when given acutely by either the intravenous or oral route. In long (...) of both these agents performed thus far indicate that the phosphodiesterase inhibitors have considerable promise for both acute and long-term treatment of patients with CHF.

1989 The American journal of cardiology

6632. Effect of phosphodiesterase inhibitors on survival of patients with chronic congestive heart failure. (Abstract)

Effect of phosphodiesterase inhibitors on survival of patients with chronic congestive heart failure. Controlled and uncontrolled hemodynamic and clinical studies have noted that the long-term treatment of patients with chronic heart failure with phosphodiesterase (PDE) inhibitors, such as amrinone, milrinone, enoximone and imazodan, may accelerate progression of the underlying disease and provoke serious ventricular arrhythmias. However, in an experimental model of chronic progressive left (...) prospectively evaluated the effect of PDE inhibition on the survival of patients with heart failure. To address this need, the Prospective Randomized Milrinone Survival Evaluation (PROMISE Trial) has been launched in 75 to 90 clinical research centers in the United States and Canada. This study will enroll 750 patients with severe (class IV) heart failure, who have symptoms refractory to conventional therapy with digitalis, diuretics, converting-enzyme inhibitor and direct-acting vasodilators. Patients

1989 The American journal of cardiology Controlled trial quality: uncertain

6633. [The anti-ischemic effect of phosphodiesterase III inhibitors]. (Abstract)

[The anti-ischemic effect of phosphodiesterase III inhibitors]. When enoximone is acutely administered to patients with stable angina and angiographically proven relevant coronary stenosis i.v. application of 0.75 mg/kg exhibits pronounced antiischemic effects. This could be observed in patients during exercise and in those in whom the ischemia was provoked by rapid cardiac stimulation. The antiischemic effects were documented by relief of symptoms, reduction of ST-depression, improvement

1994 Zeitschrift für Kardiologie Controlled trial quality: uncertain

6634. Clinical anti-inflammatory efficacy of arofylline, a new selective phosphodiesterase-4 inhibitor, in dogs with atopic dermatitis. (Abstract)

Clinical anti-inflammatory efficacy of arofylline, a new selective phosphodiesterase-4 inhibitor, in dogs with atopic dermatitis. Forty atopic dogs were studied for 28 days after the oral administration of four randomised treatments: (A) arofylline (1 mg/kg) twice daily for four weeks; (B) prednisone (0.5 mg/kg) twice daily for the first week, once a day during the second week and every 48 hours for the remaining two weeks; (C) prednisone following the same protocol but at a dose of 0.25 mg/kg

1999 The Veterinary record Controlled trial quality: uncertain

6635. Bronchodilator effect of inhaled olprinone, a phosphodiesterase 3 inhibitor, in asthmatic patients. (Abstract)

Bronchodilator effect of inhaled olprinone, a phosphodiesterase 3 inhibitor, in asthmatic patients. The effect of topical administration of phosphodiesterase (PDE) 3 inhibitors on the airway is not clear. In order to examine the usefulness of inhaled PDE3 inhibitors in the treatment of asthma, we investigated the bronchodilator effect of inhaled olprinone, a newly developed PDE3 inhibitor, in nine asthmatic patients. On three separate study days, olprinone, salbutamol, or vehicle (...) was administered in a double-blind and randomized fashion, and pulmonary functions were assessed over 60 min. Significant increases in FEV(1) were observed until 45 min after inhalation of olprinone without adverse cardiovascular effects. Mean maximal increases in FEV(1) were 16.0 +/- 4.0 and 20.5 +/- 4.2% with olprinone and salbutamol, respectively. The bronchodilator effect of olprinone was greater than that of salbutamol in four of the nine patients. These results suggest that the inhaled PDE3 inhibitor has

1999 American journal of respiratory and critical care medicine Controlled trial quality: uncertain

6636. Effects of single administration of a phosphodiesterase III inhibitor during cardiopulmonary bypass: comparison of milrinone and amrinone. (Abstract)

Effects of single administration of a phosphodiesterase III inhibitor during cardiopulmonary bypass: comparison of milrinone and amrinone. The effects of phosphodiesterase III (PDE III) inhibitors administered after aortic declamping during cardiopulmonary bypass (CPB) for open heart surgery were investigated. Ten patients (group M) were administered milrinone (50 microg/kg) after aortic declamping during CPB, 10 patients were administered amrinone (1 mg/kg) at the same time during (...) their surgery (group A), and 10 patients served as controls with no drug administered (group C). Soon after bolus infusion of the PDE III inhibitor, perfusion pressure dropped significantly in groups M and A. However, after release of CPB and at the end of surgery, there was no difference in aortic pressure between the 3 groups. There were also no differences between the groups in heart rate, pulmonary artery pressure, and pulmonary capillary wedge pressure. After weaning from CPB, the cardiac index

1999 Japanese circulation journal Controlled trial quality: uncertain

6637. Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. (Abstract)

Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. Increased cyclic AMP-phosphodiesterase activity in peripheral blood leukocytes is associated with the immune and inflammatory hyperreactivity that characterizes atopic dermatitis. Atopic phosphodiesterase has high sensitivity to a variety of enzyme inhibitors, suggesting an increased therapeutic advantage. The objective of this study was to use in vitro assays to identify a potent (...) phosphodiesterase inhibitor and then to investigate its effectiveness in treating atopic dermatitis. Leukocyte enzyme activity was measured by radioenzyme assay, whereas prostaglandin E2 and interleukins 10 (IL-10) and 4 (IL-4) were measured in 24-h culture supernatants of mononuclear leukocytes by immunoassays. The effect of a topical phosphodiesterase inhibitor on atopic dermatitis lesional skin was assessed by double-blind, paired comparisons of active drug and placebo ointments applied to symmetrically

1996 The Journal of investigative dermatology Controlled trial quality: uncertain

6638. [Hemodynamic effects of amrinone, phosphodiesterase inhibitor, early after coronary artery bypass grafting]. (Abstract)

[Hemodynamic effects of amrinone, phosphodiesterase inhibitor, early after coronary artery bypass grafting]. This study was conducted to evaluate the hemodynamic effects of amrinone early after open-heart surgery. Eighteen patients who underwent coronary artery bypass grafting were randomly divided into two groups: ten patients (group A) were administered 5 micrograms/kg/min of amrinone, and eight patients (group B) were administered 10 micrograms/kg/min. No bolus of amrinone was administered

1996 [Zasshi] [Journal]. Nihon Kyōbu Geka Gakkai Controlled trial quality: uncertain

6639. Effects of a phosphodiesterase III inhibitor on circulating blood volume after cardiopulmonary bypass. (Abstract)

Effects of a phosphodiesterase III inhibitor on circulating blood volume after cardiopulmonary bypass. Using a new method based on pulse dye densitometry, circulating blood volume (BV) was measured without direct sampling in patients undergoing open-heart surgery, and the effects of phosphodiesterase (PDE) III inhibitor administration during cardiopulmonary bypass (CPB) were evaluated. Sixteen patients scheduled for elective coronary artery bypass grafting were randomly assigned to the PDE III (...) inhibitor group or control group. BV was determined before CPB, and immediately, and 4 and 12h after operation. After declamping of the aorta, the PDE III inhibitor amrinone (1 mg/kg) was infused as a single bolus into the venous reservoir in the PDE III inhibitor group. BV decreased significantly soon after the operation in the control group. It did not decrease in the PDE III inhibitor group (48.6 +/- 44 and 60.6 +/- 8.0 ml/kg for the control and PDE III inhibitor groups. respectively). Four hours

2000 Heart and vessels Controlled trial quality: uncertain

6640. Effects of olprinone, a new phosphodiesterase inhibitor, on gastric intramucosal acidosis and systemic inflammatory responses following hypothermic cardiopulmonary bypass. (Abstract)

Effects of olprinone, a new phosphodiesterase inhibitor, on gastric intramucosal acidosis and systemic inflammatory responses following hypothermic cardiopulmonary bypass. Phosphodiesterase (PDE) III inhibitors have both an inotropic and a peripheral vasodilatory effect, and also inhibit the activation of macrophages. Thus a newly developed PDE III inhibitor, olprinone, could modify gastric intramucosal pH (pHi), systemic oxygen consumption, and systemic inflammatory responses in patients

2001 Acta Anaesthesiologica Scandinavica Controlled trial quality: uncertain

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