Plethysmographic registration of volume changes in a hand vein. Effects of serotonin and of a specific antagonist.

The influence of serotonin on a selected dorsal hand vein can be evaluated by changes in tangential wall tension, volume, and pressure. A plethysmographic method has been used to record the changes in venous capacitance at constant pressure after IV injection of small doses of serotonin. R 41 468, a specific serotonin antagonist, has been given orally (10, 20, or 40 mg) or intravenously (2.5 or 10 mg) to healthy volunteers. A reduction or a complete blockade of activity of serotonin was observed after all doses of R 41 468. Duration and strength of the antagonism were dose-dependent. This pharmacologic in vivo model allows investigations into substances with an effect on vascular smooth muscles.

Thalamonal, droperidol and fentanyl in induced hypovolaemic shock in the conscious dog.

Previous studies had shown that Thalamonal exerts a protective activity against hypovolaemic shock in experimental animals as well as in patients. The purpose of the present study was to make a long-term evaluation of the value of single doses of Thalamonal fentanyl and droperidol as shock-protecting agents in conscious dogs which received no replacement of blood loss. The study was conducted in 20 animals in which devices were implanted for measuring heart rate, arterial and venous blood pressure, left ventricular and left atrial blood pressure. The dogs were divided into 4 groups, receiving 20 ml of an i.v. injection containing either 0.025 mg/kg fentanyl, 0.625 mg/kg droperidol, 0.25 ml/kg Thalamonal (0.625 mg/kg droperidol + 0.0125 mg/kg fentanyl), or saline. Thalamonal allowed a 100 per cent survival of the dogs, one of the 5 animals survived in the droperidol group, whereas fentanyl and saline were completely ineffective. As a possible mechanism of action the interruption of the vicious sequence of blood loss, vasoconstriction and circulatory arrest at a peripheral and/or central level is discussed. The hypothesis of intracorporeal blood volume correction under the influence of Thalamonal as an anti-vasoconstrictor seems to be logical but needs further investigation.

Oxatomide in the treatment of various allergic diseases.

The use of oral oxatomide (30 to 360 mg per day) for the treatment of allergic conditions of the bronchi, skin and gastro-intestinal tract was investigated in a total of 70 subjects. Therapeutic results were evaluated at intervals ranging between 1 and 16 months. Symptomatic improvements were scored globally, forced expiratory volume in 1 second was measured in asthmatic patients, and the lesions of atopic dermatitis were rated according to a modified Clendening scale. The results suggest that oxatomide was particularly effective in the treatment of allergic rhinitis and skin allergies. Allergic asthma responded fairly well in patients with a short history of disease and gastro-intestinal conditions reacted moderately, with haemorrhagic rectitis responding better than gastritis. These findings warrant further controlled trials of oxatomide in such conditions.

Steady-state plasma levels of flunarizine in chronically treated patients.

Plasma levels were measured at different times during long-term flunarizine treatment (duration 1--45 months, median: 6 months) of 50 patients with intermittent claudication. The dose was gradually reduced, within one month, from an initial dose of 30 mg daily to a maintenance dose of 10 mg daily. Plasma levels, measured by HPLC-method, showed considerable individual differences, ranging between less than 0.02 microgram/ml and 0.25 microgram/ml. Levels between 0.05 and 0.1 microgram/ml were found in 46% of the patients. Individual measurements clearly showed dose-related plasma-levels. There were no signs of accumulation. Side-effects were related to the dose rather than to the levels. There was no correlation between clinical improvement and plasma levels. An extensive first-pass metabolism in the liver is suggested as a possible explanation for the varying inter-individual plasma levels.