Assessment of diclofenac LC50 reference values in juvenile and embryonic stages of the zebrafish (Danio rerio).

The aim of the study was to compare the acute toxicity of diclofenac to juvenile and embryonic stages of the zebrafish (Danio rerio). Acute toxicity tests were performed on the aquarium fish Danio rerio, which is one of the model organisms most commonly used in toxicity testing. The tests were performed using a semi-static method according to OECD guideline No. 203 (Fish, acute toxicity test). Embryo toxicity tests were performed in zebrafish embryos (Danio rerio) in compliance with OECD No. 212 methodology (Fish, short-term toxicity test on embryo and sac-fry stages). The results were subjected to a probit analysis using the EKO-TOX 5.2 programme to determine 96hLC50 and 144hLC50 (median lethal concentration, 50% mortality after a 96 h or 144 h interval, respectively) values of diclofenac. The statistical significance of the difference between LC50 values in juvenile and embryonic stages of Danio rerio was tested using the Mann-Whitney non-parametric test implemented in the Unistat 5.1 programme. The LC50 mean value of diclofenac was 166.6 +/- 9.8 mg/L in juvenile Danio rerio, and 6.11 +/- 2.48 mg/L in embryonic stages of Danio rerio. The study demonstrated a statistically higher sensitivity to diclofenac (P < 0.05) in embryonic stages compared to the juvenile fish.

[Pharmacology of a new antihypertensive agent, metazosin (Kenosin)]. / Farmakologie nového antihypertenzíva metazosinu (Kenosin).

Metazosin (KENOSIN) displaces 3H-prazosin from its bond to alpha-1 receptors of the cerebral cortex, antagonizes the effects of phenylephrin on spinal rats and on perfused peripheral vascular regions, which demonstrates that it is a blocker of alpha-1 adrenergic receptors. It does not affect the central alpha-2 adrenergic receptors. No peripheral antiserotonin effect was found. Metazosin decreases the blood pressure in normotensive and hypertensive animals. On intravenous administration, the decrease commences very rapidly after the onset of administration. In dogs, systolic and diastolic blood pressure, cardiac output, peripheral resistance and pressure in the pulmonary artery are decreased. In animals with experimentally increased pressure in the lesser circulation it produces a decrease in pressure. On the basis of hypotensively active doses in experimental animals, the administration of 5 mg was proposed as the clinica pose. Results of the 1st stage of clinical trials have demonstrated that this dose is effective in persons with the systolic pressure higher than 120 mm Hg. At present the effect of metazosin is tested on hypertonic patients.