摘要:

The analgesic efficacy of 50 and 100 mg tramadol and 500 and 1,000 mg metamizole was compared using a randomized double-blind design on 10 volunteers; drugs were given orally as solutions. Constant painful stimuli were applied by controlled electrical stimulation of tooth pulp. Analgesia was monitored by verbal pain rating, by measurement of the current necessary to evoke sensation in a tooth and with the aid of the amplitude of somatosensory evoked potential. All 3 analgesimetric methods showed in complete agreement higher analgesia by the 100-mg dose of tramadol compared to all other medications; 50 mg tramadol and 1,000 mg metamizole were equipotent analgesic doses. The mean relative potencies of metamizole and tramadol were found to be 1:23 in agreement with clinical studies. Pain relief was limited to 3–4 h for 100 mg tramadol; 500 and 1,000 mg metamizole and 50 mg tramadol had a shorter period of analgesi

ISSN:0031-7012    

DOI:10.1159/000138468

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Various new substituted formazans were synthesized and characterized by elemental analyses, IR and mass spectral data. The compounds were evaluated for their ability to protect against inflammation by carrageenin-induced paw edema in albino rats of either sex. The active derivatives of the present series were also tested for their analgesic activity against aconitine-induced writhing in albino mice and ulcerogenic activity in albino rats. The toxicity of the compounds was assessed by determination of their approximate LD50 on albino mice. An attempt has also been made to establish a structure-activity relationship.

ISSN:0031-7012    

DOI:10.1159/000138469

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The antagonistic effect of various antidepressants and of alprazolam on muscarinic and histamine H1 receptors has been studied in the guinea-pig ileum, and those on histamine H2 receptors on rat uterus. All antidepressants act like competitive antagonists on muscarinic and histamine H1and H2 receptors. Alprazolam has shown competitive antagonism on muscarinic and histamine H1 receptors, and noncompetitive antagonism on histamine H2 receptors. Large differences in anticholinergic activity appear between the drugs studied, whereas all of them showed a higher histamine H1 receptor antagonistic activity. Most of the drugs studied showed a histamine H2 receptor antagonistic activity similar to that of cimetidine.

ISSN:0031-7012    

DOI:10.1159/000138470

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Changes in platelet reactivity (in vivo) to adenosine diphosphate (ADP) were evaluated in intact male and female rats, gonadectomized rats (with or without hormonal treatment with oestradiol or testosterone), feminized and androgenized rats (with or without hormonal treatment with oestradiol and testosterone). The 3’,5’-cyclic adenosine monophosphate (cAMP) content of the respective platelet suspensions was also determined simultaneously. Changes recorded in platelet reactivity to ADP showed striking changes unreflective of endocrine status. No consistent concomitant changes were observed in the cAMP content of the respective platelet suspensions. The data obtained casts doubts on the presence of sexual dimorphism in platelet reactivity. A dependence of platelet reactivity on hormones per se as well as the second messenger role for cAMP in platelet reactivity also raises some dou

ISSN:0031-7012    

DOI:10.1159/000138471

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The anti-ischaemic activity of the calmodulin antagonists trifluperazine, felodipine, W-7 and calmidazolium has been investigated in electrically paced guinea-pig hearts, perfused according to Langendorff, which were subjected to 60 min of global ischaemia followed by 30 min of reperfusion. At concentrations that induced a comparable reduction in cardiac contractile force, trifluperazine, felodipine and to a lesser extent W-7, were associated with improvement of post-ischaemic functional (LVP and coronary flow) and biochemical parameters (CrP and ATP). Furthermore, felodipine and trifluperazine delayed the onset and suppressed the maximum tension of the ischaemic contracture was observed. In contrast, calmidazolium had no anti-ischaemic effects. This lack of anti-ischaemic activity of the most potent calmodulin antagonist calmidazolium, as well as the significant calcium entry blocking activity of both trifluperazine and felodipine suggest that additional factors besides calmodulin antagonism may contribute to the anti-ischaemic activity of these compounds.

ISSN:0031-7012    

DOI:10.1159/000138472

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Dihydroergotamine (DHE), administered intravenously to pithed normotensive rats, increased the mean arterial blood pressure dose-dependently. This pressor effect was noncompetitively inhibited by the 5-hydroxytryptamine (5-HT) receptor antagonists pizotifen and cyproheptadine (0.1 mg/kg each). The α1-adrenoceptor blocker prazosin (1 mg/kg) had no influence on the DHE effect whereas the α2-adrenoceptor blocker yohimbine, at the same dose, proved to be a noncompetitive inhibitor of this pressor effect. The results indicate that both the 5-HT receptors and α2-adrenoceptors are involved in the DHE-induced vasoconstriction. On the other hand, in pithed normotensive rats, DHE proved to be a potent inhibitor of the pressor response to 5-HT but it did not inhibit that to noradrenaline. The results obtained characterize DHE as a noncompetitive dualist at vascular 5-HT recepto

ISSN:0031-7012    

DOI:10.1159/000138473

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The present study was designed to examine the effects of two new angiotensin-converting enzyme (ACE) inhibitors, CGS 14831 and CGS 16617 (3 mg/kg i.v. 1 min prior to occlusion and 4 and 24 h after occlusion), on myocardial ischemic (MI) damage and left-ventricular hypertrophy in rats. Administration of CGS 14831 or CGS 16617 inhibited angiotensin-1-induced pressor responses by 40–100% for 4 h after each dose. Myocardial creatine phosphokinase (CK) levels were 10.6 ± 0.6 U/mg protein in sham-MI animals, and following coronary artery occlusion for 48 h were decreased to 4.1 ± 0.2 U/mg protein in MI + vehicle animals (p < 0.01). CGS 14831 and CGS 16617 attenuated the decrease in CK content and resulted in 47 and 40% sparing, respectively, of the left-ventricular free wall. Neither agent attenuated the left-ventricular hypertrophy which developed following coronary artery occlusion. These data indicate that the nonsulfhydryl ACE inhibitors CGS 14831 and CGS 16617 have a significant cardioprotective effect in rats surviving 48 h, and suggest a potential therapeutic usefulness of these agents for the treatment of ischemia-induced heart fail

ISSN:0031-7012    

DOI:10.1159/000138474

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

A rise in blood and liver acetaldehyde concentrations following an intragastric administration of ethanol to rats was significantly inhibited when the quinone derivatives 2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone (ubidecarenone, coenzyme Q10), 4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-fJquinoline-2,7,9-tricarboxylicacid(pyrroloquinoline quinone, PQQ) and 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone) were injected intraperitoneally, prior to ethanol load, at a dose of 10, 11.5 and 30 mg/kg of body weight, respectively. When acetaldehyde was incubated in vitro with 1,4-benzoquinone (3.7–13.0 mM) or PQQ (1.4–4.9 mM) at 0 and 40 °C, the acetaldehyde concentrations slowly decreased with incubation time at 40 °C. The results suggest that low acetaldehyde concentrations following ethanol load are due to an accelerated oxidation of acetaldehyde by PQQ in the liver and the circulating

ISSN:0031-7012    

DOI:10.1159/000138475

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The transport of organic anions by the kidney has been shown to be a carrier-mediated process. In an effort to learn more about this process, and examine the potential for two organic anions to compete for the same carrier site, studies were done which involved the transport of p-aminohippuric acid (PAH) and furosemide by vesicles made from basal-lateral membranes of rabbit kidney proximal tubules. Basal-lateral membranes were prepared by differential and ultracentrifugation. The transport was measured by using radiola-belled (3H) organic anions. The transport of each molecule was inhibited by probenecid, indicating that the carrier-mediated process for organic anion transport was functional in these studies. The results indicate that transport of PAH can be inhibited by furosemide in a concentration-dependent manner. This may indicate competition for the same carrier site. Inhibition of furosemide transport by PAH was not significant, perhaps due to much variability in the data. This variability may be due to nonspecific binding of furosemide to the vesicle, higher affinity of furosemide than of PAH for the receptor, or to the presence of more transport carriers for furosemide than for PAH. Experiments were done to determine the extent of nonspecific binding of furosemide. The results show that nonspecific binding of furosemide is extensive, indicating that this may contribute to the differences seen in the inhibition of transport. The data suggest that PAH and furosemide are transported by a common carrier-mediated process in the proximal tubule of the rabbit kidney.

ISSN:0031-7012    

DOI:10.1159/000138476

出版商:S. Karger AG    

年代:1988

数据来源: Karger