Polish journal of pharmacology and pharmacy最新文献

The effect of 8-OH-DPAT, a 5-HT1A receptor agonist, on the locomotor activity was analyzed in Albino Swiss mice. The studied drug (0.5-5 mg/kg) inhibited the spontaneous locomotor activity in mice. The hypoactivity induced by 8-OH-DPAT (1.5 mg/kg) was abolished by the dopamine (D1 and D2) receptor antagonist-haloperidol (0.00125 and 0.0025 mg/kg, but not in higher doses) and by the D2 antagonist with affinity for 5-HT1A and 5-HT2 receptors-spiperone (0.0025 and 0.005 mg/kg, but not in higher doses). The effect of 8-OH-DPAT was slightly reduced by the alpha 2-adrenoceptor antagonists: idazoxan (4 mg/kg), yohimbine (2 and 4 mg/kg) and rauwolscine (4 mg/kg). On the other hand, the non-selective 5-HT antagonist metergoline (0.5-4 mg/kg), the 5-HT1A antagonist NAN-190 (0.5-2 mg/kg), the beta-adrenoceptor blockers with high affinity for 5-HT1A and 5-HT1B receptors: pindolol and SDZ 21009 (2-8 mg/kg) and the agonist/antagonist of 5-HT1A receptors ipsapirone (2.5 and 5 mg/kg) did not affect the 8-OH-DPAT-induced hypoactivity. The obtained results suggest that the reduction of the spontaneous locomotor activity induced by 8-OH-DPAT results from a stimulation of dopamine autoreceptors, but not 5-HT receptors. Involvement of an alpha 2-adrenergic mechanism cannot be excluded.

A relatively simple assay for determining the capability of chemicals to induce the reactivation of UV-irradiated pseudorabies virus in human embryo cells is presented. Using this assay cyclophosphamide (CP) and diethylstilbestrol (DES) were tested in the presence and in the absence of exogenous metabolizing system. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was used for comparison. CP increased the survival of UV-irradiated pseudorabies virus exclusively in the presence of exogenous metabolizing system. In the cells pretreated with CP or MNNG the survival of the virus was dependent on time interval between host cell pretreatment and virus infection. No enhancement of virus survival was obtained in the cells pretreated with DES.

The effect of xanthotoxol (8-hydroxypsoralen) on proliferation of TCTC cells in vitro has been studied. Xanthotoxol at concentrations of 5 to 50 micrograms/ml inhibited the growth of cells. In cultures with xanthotoxol, decreased amount of cell protein, mitotic index, and decreased ability to form a colony, were observed. Moreover, xanthotoxol disturbed mitoses elevating the number of mitotic cells in the telophase stage. An increase of giant and multinuclear cells was also found. On the basis of these results it can be concluded, that 8-hydroxypsoralen which in comparison with other psoralens is not sensitive to photostimulation, inhibits the cell proliferation anyway. This fact shows that the mechanism of the psoralens activity is to some extent independent from the photostimulation.

Numerous experimental data obtained in the studies of factors influencing the transfer of model drugs (diazepam, inulin, hippurate) into the lymphatic system were evaluated using compartmental pharmacokinetic analysis. The selection of kinetic equations for lymphatic data analysis in respect to blood ones is specific. Lymphatic kinetic equations correspond in every case tested with those used generally in blood kinetic analysis of drugs administered perorally. The lag time parameter is useful in this lymphatic analysis, too.

Twenty one derivatives of 2,3-dihydroimidazo[1,2-a]pyrimidine-6-carboxylic acid (6 n-butyl amides and 15 free acids) bearing the aromatic ring in position 1 or 2 were obtained. They were synthesized by aminolysis or hydrolysis of respective ethyl esters. Pharmacological studies on the central action of eight compounds 1, 2, 4, 5, 7, 8, 9 and 10 were carried out on mice and rats. The most active compounds, producing sedation and hypothermia, and 1, 2 and 5. The compounds decreased amphetamine-induced hyperactivity. Besides, compound 2 exerted analgesic effect in mice.

Scyliorhinin I, a decapeptide, of tachykinin family, and its two analogs containing Val or Ile in position 7, have been synthesized using the solid-phase method, and tested for agonistic activity on isolated guinea pig ileum. Both analogs were slightly more active than scyliorhinin I, but they were significantly less potent than substance P.

Quantitative structure-activity relationships (QSAR) were analyzed for 5-HT1 and 5-HT1A affinity data of two series of 1-arylpiperazines. A conformational analysis of the investigated derivatives was performed using CNDO/2 method. It was shown that some 1-arylpiperazines adopt the bioactive conformations, while the others, like 1-(2-alkylphenyl)-piperazines, should exist in the twisted conformations at the receptor sites.

A fourteen-days treatment (twice a day) of male Wistar rats with the putative anxiolytic ipsapirone (10 mg/kg po) and the selective 5-HT1A agonist 8-OH-DPAT (1 mg/kg ip) induced changes in the turnover of serotonin and catecholamines in various regions of the brain. In contrast to 8-OH-DPAT, ipsapirone stimulated the development of tolerance in serotonin neurons in the hypothalamus, hippocampus, cortex and striatum. Nevertheless, adaptative changes were not produced by ipsapirone in dopamine neurons in the striatum or nucleus accumbens, or in noradrenaline neurons in the hypothalamus, hippocampus or cortex. The centrally active metabolite of ipsapirone 1-PP, which has adrenolytic properties, seems to be responsible for the effects on the dopamine and noradrenaline turnover.

Reserpine ulcers were produced in dependent and withdrawal rats. The reactivity of isolated duodenum and colon to morphine and papaverine was tested in both groups of animals. Chronic administration of morphine decreases the development of post reserpine gastric ulcers, while in withdrawal rats it increases their occurrence. Relaxation and contraction responses of duodenum taken from the dependent rats showed tolerance. On the other hand, withdrawal rats displayed increased responses as compared with placebo group. Colon of dependent rats showed stronger responses to morphine and papaverine which indicates the lack of tolerance to morphine or enhanced receptors sensitivity. Stronger responses of colon in both dependent and withdrawal rats suggest the lack of tolerance in this segment of the gut. In withdrawal rats which obtained reserpine and placebo responses to papaverine were similar. It is suggested that reserpine decreased the sensitivity of mu receptor to morphine.

SP-antagonistic properties of a newly synthesized peptide Tyr-Pro-D-Phe-Phe-D-Phe-D-Trp-MetNH2 (AWL-60) were investigated both in vitro and in vivo. In vitro AWL-60 effectively antagonized the action of SP-agonist (SP6-11); however, this antagonism was non-competitive. Antagonistic properties of AWL-60 were also observed in vivo: in doses as low as 0.1 nmol/kg iv AWL-60 markedly attenuated the fall in blood pressure produced by [less than Glu]6SP6-11. Since AWL-60 exerts weak opioid agonistic properties (as a casomorphine analog) the possible involvement of an opioid agonistic component in their SP inhibitory action is considered.