Effect of liver impairment on the pharmacokinetics of tolcapone and its metabolites.

Objective: To assess the effect of liver impairment on the pharmacokinetics of tolcapone and to derive appropriate dose recommendations for patients with this disease who are undergoing treatment for Parkinson's disease.

Study Design: In an open, two-way crossover study, 16 patients with moderate liver disease (eight with cirrhotic and eight with noncirrhotic liver disease) and eight healthy subjects received an oral dose of 200 mg tolcapone and an intravenous dose of 50 mg tolcapone on separate occasions. The concentrations of total and unbound tolcapone and its three major metabolites (tolcapone glucuronide, carboxylic acid, and 3-O-methyl metabolite) were assessed in plasma and urine.

[Endothelins: possibly a new pharmacological approach in cardiovascular diseases, kidney diseases and oncological disorders].

Only 10 years ago, the vasoconstricting peptide endothelin was discovered; it is produced by endothelial cells. Different isoforms and receptors of endothelin have been identified. The effects of endothelin-I, the most important isoform, are mainly vasoconstriction and proliferation of cells.

Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension.

We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week.

Neurohypophyseal hormones and excessive grooming behaviour.

The pattern of excessive grooming displayed by rats treated with vasopressin and oxytocin was investigated by calculating the frequencies and contribution of the behavioural elements head washing, body grooming, anogenital grooming, paw licking and scratching. In addition, the suppressive effect on peptide-induced grooming of the dopamine D1 receptor antagonist SCH 23390, of neurotensin and of the opiate receptor antagonists naloxone and naloxone-methobromide was studied. The pattern of excessive grooming induced by vasopressin and by oxytocin was characterized by the contribution of most behavioural elements to the total grooming scores.