GAL-021, a new intravenous BKCa-channel blocker, is well tolerated and stimulates ventilation in healthy volunteers.

Background: Potassium-channels in the carotid body and the brainstem are important regulators of ventilation. The BKCa-channel contains response elements for CO, O2, and CO2. Its block increases carotid body signalling, phrenic nerve activity, and respiratory drive.

No pharmacokinetic interaction between paliperidone extended-release tablets and trimethoprim in healthy subjects.

Objective: The effect of trimethoprim, a potent organic cation transport inhibitor, on the pharmacokinetics (PK) of paliperidone extended-release tablets (paliperidone ER), an organic cation mainly eliminated via renal excretion, was assessed.

Methods: Open-label, two-period, randomized, crossover study in 30 healthy males. Single dose of paliperidone ER 6 mg was administered either alone on day 1 or day 5 during an 8-day treatment period of trimethoprim 200 mg twice daily.

Correlations between factors determining the pharmacokinetics and antiviral activity of HIV-1 non-nucleoside reverse transcriptase inhibitors of the diaryltriazine and diarylpyrimidine classes of compounds.

Objective: To investigate the important factors that determine the bioavailability and the antiviral activity of the diaryltriazine (DATA) and diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1 in animal species and humans using cell-based assays, physicochemical and computed parameters.

Methods: This naturalistic study included 15 parameters ranging from molecular mechanics calculations to phase I clinical trials. The calculated parameters were solvent-accessible surface area (SASA), polar surface area and Gibbs free energy of solvation.

The metabolism and excretion of galantamine in rats, dogs, and humans.

Galantamine is a competitive acetylcholine esterase inhibitor with a beneficial therapeutic effect in patients with Alzheimer's disease. The metabolism and excretion of orally administered (3)H-labeled galantamine was investigated in rats and dogs at a dose of 2.5 mg base-Eq/kg body weight and in humans at a dose of 4 mg base-Eq.

The effect of ketanserin, a 5-HT2-receptor antagonist, on 5-hydroxytryptamine-induced irreversible platelet aggregation in patients with cardiovascular diseases.

Platelet aggregation in response to 5-hydroxytryptamine was investigated in 40 normal subjects, in 45 patients with acute myocardial infarction, and in 65 patients with peripheral arterial obstructive disease. It was found that of the 110 patients with cardiovascular disease, 40% had a biphasic irreversible platelet aggregation, whereas this phenomenon occurred in only 7.5% of the normal population.

Comparison of blood pressure ratio by Doppler velocimetry and by plethysmography during treatment with ketanserin, a 5-HT2 receptor antagonist: a measure of improved collateral and microcirculatory flow.

We could demonstrate a progressive and significant increase in blood pressure ratio (thigh/arm) in 42 patients with intermittent claudication, treated with ketanserin for 9 months, which confirms our earlier double-blind placebo-controlled findings. In an additional experiment comparing blood pressure ratio with Doppler velocimetry and with plethysmography, an upwards shift was observed for the plethysmographic values as compared with the Doppler values during ketanserin therapy, and only at the level of the thigh, which suggests an improvement of the collateral and microcirculatory flow.

Ketanserin and red blood cell sodium content in hypertension.

The sodium content of erythrocytes from patients with essential hypertension is increased. In a double-blind, placebo-controlled study, a 5-day treatment with ketanserin, a serotonergic antagonist lowered significantly the sodium content of the red blood cells (RBC). Ouabain induces an increase of sodium content of the RBC, which is paralleled by a decrease in RBC deformability.

Effect of ketanserin on the hyperreactivity of platelets to 5-hydroxytryptamine in patients with cardiovascular diseases.

Platelet aggregation in response to 5-hydroxytryptamine (5-HT) was investigated in 110 patients with cardiovascular diseases and in 40 age-matched control subjects. It was found that 40% of those patients had a biphasic irreversible platelet aggregation in response to 5-HT, whereas 92.5% of the control subjects responded with a weak reversible aggregation.

Placebo-controlled double-blind trial of ketanserin in treatment of intermittent claudication.

Ketanserin, a selective serotonin (5-HT) antagonist at 5-HT2 receptors, was investigated in a 3-month, double-blind, placebo-controlled study in twenty patients with intermittent claudication. Blood-pressure ratio (thigh/arm), reactive hyperaemia measured with an ECG-triggered venous occlusion plethysmograph, blood filterability, and claudication distance on a treadmill progressively and significantly improved during ketanserin therapy, whereas no such changes occurred in the placebo group. Mean claudication distance improved by 140%; four of the eleven patients on ketanserin were able to keep walking beyond the time limit of the exercise test.

Enumeration of T-lymphocytes and T-lymphocyte subsets in rheumatoid arthritis using monoclonal antibodies.

The number of T-lymphocytes and T-lymphocyte subsets was measured in peripheral blood of 51 patients with rheumatoid arthritis. T-lymphocytes were counted by E-rosette tests and by the immunogold staining method with OKT3.PAN monoclonal antibody.

The antihypertensive effects of a pure and selective serotonin-receptor blocking agent (R 41 468) in elderly patients.

In a first experiment, an acute intravenous administration of 10 mg R 41 468, a pure serotonin-receptor blocking agent with high selectivity for blood vessels and thrombocytes and devoid of central effects, dramatically reduced systolic and diastolic blood pressure in 23 elderly hypertensive patients. Heart rate and cardiac output remained virtually unchanged. In a second double-blind placebo-controlled cross-over study a highly significant decrease of systolic and diastolic blood pressure was obtained in 14 elderly hypertensive patients during an 8-day oral treatment with 40 mg t.