Journal de pharmacologie最新文献

In vitro experiments were conducted on the inhibitory properties of extracts from Ribes nigrum L. and Alchemilla vulgaris L. (fractions A1 + A2, A1, A2) on activity of the proteolytic enzymes elastase, trypsin and alpha-chymotrypsin. Extracts from Ribes Nigrum L. and Alchemilla Vulgaris L. (Fraction A1) inhibited 50% of the activity of porcine pancreas elastase at concentrations of 0.56 mg/ml and 0.16 mg/ml, respectively, against a synthetic substrate. Inhibition was less effective on activity of trypsin and alpha-chymotrypsin. Marked in vivo angioprotective properties were shown by the compounds studied, except Fraction A2 of Alchemilla vulgaris L. which had no significant activity. The results suggest a possible role by these inhibitors in the protection of conjunctive and elastic tissues adversely affected by proteolytic enzymes. An additional advantage is their lack of toxicity.

In rat cerebral cortex, the 3H-Nicergoline (an ergot alkaloid derivative) binding was rapid, reversible, saturable and of high affinity. In various structures of the central nervous system except midbrain and cerebellum, the maximum binding capacity (B max) for 3H-Nicergoline is greater that for 3H-Prazosin. The specificity studies of 3H-Nicergoline binding show interactions with alpha 1-adrenergic and serotoninergic receptors. These results are confirmed after irreversible blockade with phenoxybenzamine. In conclusion, as nicergoline is known to cross the blood-brain barrier, this study shows that it exerts its central action on alpha 1-adrenoceptors as well as serotoninergic receptors.

The following psychopharmacological effects of adrafinil have been observed in mice: increase in locomotor activity (64-256 mg.kg-1), antagonism (16-128 mg.kg-1) of the hypnotic effects of barbitone but not of pentobarbitone, reduction of immobility duration in the forced swimming test (16-256 mg.kg-1); slight antagonism (256 mg.kg-1) of electroshock-induced convulsions; no modification of rectal temperature; no stereotyped or climbing behaviour; no increase in lethality in aggregated mice (LD50 isolated = 1022 mg.kg-1, LD50 aggregated = 859 mg.kg-1); lack of effects on the provisional tests for antidepressants: no interaction with reserpine-, oxotremorine-, or apomorphine-induced hypothermia but potentiation of yohimbine-induced toxicity; lack of peripheral sympathetic effects (no mydriasis, no salivation, no contraction of the pilomotor muscles, no antagonism of reserpine-induced ptosis); lack of peripheral anticholinergic effects (no mydriasis, no antagonism of oxotremorine-induced salivation or lacrimation). As compared to no analeptic, anticholinergic or antidepressant drugs, adrafinil shows a unique behavioural profile in mice defined on the one hand by a specific stimulant activity associated with antidepressant-like effects that do no seem related to a beta-adrenergic mechanism and on the other hand by a lack of dopaminergic effects. Most adrafinil-induced effects (increase in locomotor activity, reduction of immobility duration in the forced swimming test) may correspond to a central alpha 1-adrenergic stimulation, but the unexpected lack of peripheral sympathetic effects remains unexplained.

The cardiovascular effects of nicergoline, a preferential alpha 1-adrenoceptor blocking drug, were studied in anaesthetized normotensive or spontaneously hypertensive (SH) rats. Nicergoline (300 micrograms/kg, i.v.) significantly reduced blood pressure and heart rate in control, bivagotomized or beta-blocked normotensive or SH rats. In bilaterally vagotomized and beta-blocked rats, nicergoline reduced mean blood pressure but did no longer modify heart rate. Thus, it is postulated that nicergoline could reduce the sympathetic tone and increase the vagal nerve activity, possibly by inhibiting central alpha 1-adrenoceptors. The nicergoline--induced bradycardia was greater in bivagotomized SHR than in normotensive ones. Intracerebroventricular injections of nicergoline (30 micrograms/kg) did not modify heart rate in normotensive control, bivagotomized or beta-blocked rats. On the contrary, nicergoline (30 micrograms/kg) injected into the cisterna magna induced a significant bradycardia in the three groups of normotensive rats. Blood pressure was reduced in the same way in all groups centrally treated by nicergoline. In conclusion, it seems that nicergoline reduces blood pressure by peripheral alpha-adrenoceptor blockade and modulates the autonomic nervous activity by inhibiting alpha 1-adrenoceptors mainly localized in the brainstem.

The pharmacokinetics of daunorubicinol (DOL), the main metabolite of daunorubicin (DNR), was studied in rabbits and compared to that of daunorubicin after an 8 mg/kg dose. High-performance liquid chromatography was used to separate parent drug and metabolites. The plasma disappearance of DNR and DOL was triexponential. DOL was the major species detected in plasma and urine. Both drugs had large volumes of distribution. About 70% of DNR or DOL were bound to plasma proteins and mainly to albumin. Pharmacokinetic parameters of DOL obtained after injection of DOL were different from those calculated for DNR and those calculated for DOL after injection of DNR. The total urinary excretions of DNR or DOL were similar and amounted to 25% of the dose. No conjugates were identified in urine after enzymatic treatment. No fluorescent drug was identified in the feces. Anthracyclines were degraded in vitro in rabbit feces. The rabbit seems to be a good model for the study of anthracycline pharmacokinetics as our results in rabbits after DNR injection were similar to those in human studies.

The discovery of monoclonal antibodies has brought about a revolution in diagnostic and therapeutic. New antigens have been discovered on cell surfaces allowing the fine classification of cell lineages. Leukemia cells and tumors can now be characterized accurately. Regarding in vitro diagnostics monoclonal antibodies have allowed uniform standardization and a rational approach to hormone polymorphism. Monoclonal antibodies are now tested as pharmacological drugs. They have proved their use in the prevention and cure of rejection in bone marrow and kidney transplantation.