Search results for "Piperidines"

Human cerebral microcirculation and oxygen saturation during propofol-induced reduction of bispectral index †

2011

† This study investigates the effects of propofol-induced changes in bispectral index (BIS) on cerebral microcirculation and oxygenation during craniotomies. † In 2 mm cerebral depth, an increase in propofol dosage resulted in increased oxygen saturation (srvO2 )w ithout reduction of capillary venous blood flow (rvCBF). † Difference in oxygen content (avDO2) and approximated cerebralmetabolicrateofoxygen (aCMRO2) decreased with an increase in propofol dosage in 2 mm cerebral depth. † Alterations in BIS showed no effect on rvCBF, srvO2 ,a nd haemoglobin amount (rvHb) or on avDO2 or aCMRO2 in 8 mm cerebral depth. † These findings suggest that the CBF/CMRO2 ratio is altered by propofol in a re…

Efficacy and tolerability of lasmiditan, an oral 5-HT1F receptor agonist, for the acute treatment of migraine : a phase 2 randomised, placebo-control…

2012

Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study. We aimed to assess the efficacy and safety of oral lasmiditan for the acute treatment of migraine.In this multicentre, double-blind, parallel-group, dose-ranging study in 43 headache centres in five European countries, patients with migraine with and without aura and who were not using prophylaxis were randomly assigned (1:1:1:1:1) to treat one moderate or severe attack at home with 50 mg, 100 mg, 200 mg, or 400 mg lasmiditan, or placebo. Study drug and placebo were sup…

Spinal Endocannabinoids and CB 1 Receptors Mediate C-Fiber–Induced Heterosynaptic Pain Sensitization

2009

Plastic Pain Perception Drugs and endocannabinoids acting on cannabinoid (CB) receptors have potential in the treatment of certain types of pain. In the spinal cord they are believed to suppress nociception, the perception of pain and noxious stimuli. Pernia-Andrade et al. (p. 760 ) now find that endocannabinoids, which are released in spinal cord by noxious stimulation, may promote rather than inhibit nociception by acting on CB1 receptors. Endocannabinoids not only depress transmission at excitatory synapses in the spinal cord, but also block the release of inhibitory neurotransmitters, thereby facilitating nociception.

Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma : results From the Open-Label, Multicenter, Phase II DAWN Study

2018

Purpose The Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated clinical activity in B-cell malignancies. The DAWN study assessed the efficacy and safety of single-agent ibrutinib in chemoimmunotherapy relapsed/refractory follicular lymphoma (FL) patients. Methods DAWN was an open-label, single-arm, phase II study of ibrutinib in patients with FL with two or more prior lines of therapy. Patients received ibrutinib 560 mg daily until progressive disease/unacceptable toxicity. The primary objective was independent review committee–assessed overall response rate (ORR; complete response plus partial response). Exploratory analyses of T-cell subsets in peripheral blood (baseline/cycle …

Lorcainide; II. Plasma concentration-effect relationship

1979

Time Course of 5-HT2A Receptor Occupancy in the Human Brain after a Single Oral Dose of the Putative Antipsychotic Drug MDL 100,907 Measured by Posit…

1997

MDL 100,907 is a potent and selective antagonist of 5-HT2A serotonin receptors. Animals studies suggest that MDL 100,907 may behave as an atypical antipsychotic drug. Positron emission tomograph (PET) using [11C]NMSP as the radiotracer was used to define the time course of 5-HT2 receptor occupancy in the human frontal cerebral cortex after a single oral dose of MDL 100,907 (10 or 20 mg) in nine healthy subjects. After the baseline scan each subject was studied three times post dosing at various time points. 5-HT2 occupancies were in the range of 70 and 90% after each dose. While the occupancy remains in this range over 24 hours after 20 mg MDL 100,907, it decreases by about 20% at 24 hours …

Effect of intravenous flecainide on atrial vulnerability in man.

1985

Sixteen patients were investigated by means of programmed atrial stimulation at 2 different driving rates: 100/min and 120/min. All patients had an increased atrial vulnerability at both driving rates. After the administration of intravenous flecainide (1 mg/kg bodyweight as a bolus, followed by the same amount infused over a period of 20 minutes), the increased vulnerability was abolished in 11 and 9 patients, respectively. In the remaining patients the rate of induced atrial tachyarrhythmia decreased. These findings correlate with a significant prolongation of the effective refractory period of the right atrium and a corresponding significant shortening of its relative refractory period. …

Effect of intravenous flecainide on atrial vulnerability in man.

1983

Sixteen patients were investigated by means of programmed atrial stimulation at two different driving rates: 100 and 120/min. All patients had an increased atrial vulnerability at both driving rates. After intravenous flecainide application (1 mg/kg body weight as a bolus followed by the same amount given by infusion over a period of 20 min) the increased vulnerability was abolished in 11 and 9 patients respectively. In the remaining patients the rate of induced atrial tachyarrhythmia decreased. These findings correlate with a significant prolongation of the effective refractory period of the right atrium and a significant shortening of the relative refractory period of the right atrium. It…

Haemodynamic effects of a single intravenous dose of lorcainide in patients with heart disease

1980

The cardiovascular effects of a single i.v. dose (2 mg/kg over 5 min) of lorcainide were studied in 14 patients with heart disease. In the haemodynamic part of the study (6 patients), the aortic and pulmonary systolic, diastolic and mean pressures, left ventricular systolic and end-diastolic pressures, cardiac output and the rate of rise of left ventricular pressure were measured before and for 30 min after administration of the drug. Lorcainide produced a slight and short-lasting decrease in the aortic and pulmonary systolic pressures, and all other pressure values remained unchanged. The cardiac output and systemic vascular resistance were not altered by lorcainide. It consistently depres…

Experience in the long term use of new antiarrhythmic drugs.

1985

Meinertz et a1. (1984) investigated the long term efficacy and tolerability of flecainide in patients with ventricular arrhythmias. 15 patients were studied, 8 women and 7 men, aged 19 to 74 (mean 58.7) years, with more than 30 ventricular premature complexes (VPCs) per hour, and ventricular arrhythmias of Lown grade IVA or IVB. 11 had coronary artery disease and 2 had idiopathic dilated cardiomyopathy. Patients were excluded on the basis of sustained ventricular tachycardia (VT) [defined as ~ 3 consecutive beats at a rate of> 100 beats/min]; myocardial infarction within the last 6 months; unstable angina; severe congestive heart failure; or conduction abnormalities. Previously unsuccessful…