Polish journal of pharmacology and pharmacy最新文献

A quantitative analysis of biologically active sesquiterpene lactones in ethanol and aqueous extracts of Chrysanthemum parthenium and its form flosculosum was carried out. The sesquiterpene lactone contents in the extracts were comparable, although the contents of ethanol extracts (ca. 0.5%) were higher than of aqueous ones (ca. 0.3%). Parthenolide was found to be the main constituent of the lactones. The applied IR and TLC/FID methods for quantitative determination of the total sesquiterpene lactones and parthenolide, respectively, may be used for chemical standardizing of the raw material and its preparations.

Antidepressant neuroleptics, perazine (PZ), levomepromazine (LMZ) and flupenthixol (FPX) given to rats jointly with imipramine (IMI) for 2 weeks affected the plasma concentration of IMI only slightly but markedly elevated the concentration of its metabolite, desipramine (DMI). In the brain PZ significantly elevated both IMI and DMI concentrations while LMZ and FPX showed a tendency to increase the concentration of IMI and decrease the concentration of DMI. All three neuroleptics markedly decreased the DMI/IMI ratio in the brain and (except FPX) increased it in the plasma. Given alone for two weeks PZ, LMZ, FPX did not affect the levels of cytochromes P-450 and b-5 in liver microsomes. Chronic treatment with IMI significantly elevated the concentration of cytochrome P-450 in the liver and had a tendency to increase the concentration of cytochrome b-5. FPX, but not PZ or LMZ abolished this effect. Neuroleptics coadministered with IMI to rats did not affect the activity of the enzymes responsible for the IMI biotransformation as compared with IMI-treated animals. The neuroleptics added to the incubation mixture in vitro inhibited IMI hydroxylation noncompetitively. The demethylation was inhibited competitively by LMZ but noncompetitively by PZ and FPX. The inhibitory effect of neuroleptics on the hydroxylation was much more marked than that on the demethylation. FPX was the weakest inhibitor of IMI metabolism among the neuroleptics studied.

The characteristics of [3H]prazosin binding sites in the membranes from cerebral cortex, the basal level of formation of cyclic AMP in cortical slices, and the responsiveness of the cyclic AMP generating system to noradrenaline and isoproterenol in this preparation were measured in Long-Evans, Wistar and Sprague-Dawley rats treated chronically with saline or imipramine. No differences between strains and treatments were observed regarding the Bmax and KD of [3H]prazosin binding sites. The basal levels of cyclic AMP formation were similar in control rats of all strains, but imipramine treatment augmented it significantly in Sprague-Dawley rats. The responses of the cyclic AMP generating system to noradrenaline were significantly lower in Long-Evans than in the remaining strains of rats. Only in Sprague-Dawley rats a significant downregulation of response to noradrenaline was observed after imipramine treatment. All three strains of rats differed significantly among themselves in their responsiveness to isoproterenol; only in Sprague-Dawley rats this response was down-regulated significantly (by 80%) by imipramine treatment.

Nifedipine (2.5-10 mg/kg) and verapamil (2.5 and 10 mg/kg) offered some protection against pentylenetetrazol (100 and 130 mg/kg)-induced seizure activity in mice. No protection was provided by diltiazem (1.25-10 mg/kg) in this model of experimental epilepsy. Repeated administration of calcium channel blockers (CCBs) in doses of 5 and 10 mg/kg twice daily for three days resulted in no protective effect against pentylenetetrazol. Regarding electroconvulsions, nifedipine (2.5-10 mg/kg) showed the best anticonvulsive action--for instance, in the dose of 10 mg/kg (60 min--treatment time) it elevated the threshold for electroconvulsions from 7.1 to 10.5 mA. Diltiazem (up to 10 mg/kg) and verapamil (up to 20 mg/kg) were considerably less potent in this respect. After repeated administration, only nifedipine (5-10 mg/kg) retained its protective action against electroconvulsions.

In aqueous solutions ultrasounds are known to generate oxygen free radicals. Here we report that ferricytochrome c and nitroblue tetrazolium when sonificated in 1% ethanolic buffered solutions are reduced predominantly in a SOD-inhibitable manner. Aqueous solutions of adrenaline undergo oxidation when exposed to ultrasounds. Therefore, it seems that in the presence of ethanol or adrenaline ultrasounds generate substantial amounts of superoxide anions along with other free radicals. We have tried to adapt ultrasound technique for detection of scavenging of superoxide anions by a metabolite of molsidomine, SIN-1 and flavonoids. In the presence of SIN-1 reduction of indicators by superoxide anions generated by ultrasounds was prevented. In the case of quercetin we failed to detect this property because ultrasounds were found to transform native flavonoids into oxidized derivatives.

Synthesis of four new derivatives of enkephalin analogs: H-BuTyr-DMet-Gly- Phe-epsilon Ahx-OH 9, H-BzlTyr-DMet-Gly-Phe-epsilon Ahx-OH 12, H-Butyr-DMet-Gly- -Phe-epsilon Ahx-epsilon Ahx-OH 15 and H-BzlTyr-DMet-Gly-Phe-epsilon Ahx-OH is reported. They were examined for agonistic, antagonistic and analgesic activity. Compound 12 is the most potent among investigated peptides. Its agonistic activity in vitro is 7.85 x 10(-8) M/l (GPI) and 9.5 x 10(-7) M/l (MVD). None of the peptides showed antagonistic activity. Only compound 12 showed weak, not dose-dependent analgesic activity in rats.

Two new derivatives of benzazocine of anticipated analgesic action were synthesized. Pharmacological investigations were carried out to confirm their analgesic activity, affinity to the opiate receptor and potential antagonistic properties.

Buthobendin activated glycolytic lactate formation stronger than epinephrine and increased the ATP level, both in vitro in rabbit myocardial slices and in vivo in rabbit blood. These effects were accompanied by an increase in extracellular magnesium concentration, which was probably related to the inhibitory effect of buthobendin on the membrane-bound ATPases.

The DNA synthesis inhibition test and the DNA repair test have been used to study the effects of interaction between busulfan and DNA synthesis in two cell systems in vitro. The results of this study indicate that busulfan at concentration 500 and 1000 micrograms/ml damages mouse and human embryo cells. They also suggest that mouse embryo cells are unable to repair this damage.