Efficacy of senna versus lactulose in terminal cancer patients treated with opioids.

The best laxative for terminal cancer patients treated with opioids still remains to be determined. This comparative study was conducted with the objective of determining treatment and cost efficiency for senna and lactulose in terminal cancer patients treated with opioids. The methodology used a randomized, open, parallel group design. The study was conducted in the Palliative Care Unit in one Madrid Health Care District. Ninety-one terminal cancer patients were randomized into two groups: A = treated with senna (starting with 0.4 mL daily), and B = treated with lactulose (starting with 15 mL daily) for a 27-day period. The main outcome measures were defecation-free intervals of 72 hr, days with defecation, general health status, and treatment cost. Laxative efficacy was analyzed through t test and analysis of variance. No difference was found between the laxatives in defecation-free intervals or in days with defecation. The final scores for general health status were similar in both groups. Given that the two treatments have similar efficacy and adverse effects, a recommendation is made for the use of senna because its cost is lower than lactulose.

7-[3-(1-piperidinyl)propoxy]chromenones as potential atypical antipsychotics. 2. Pharmacological profile of 7-[3-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)-piperidin-1-yl]propoxy]-3-(hydroxymeth yl)chromen -4-one (abaperidone, FI-8602).

A series of novel 7-[3-(1-piperidinyl)propoxy]chromenones was synthesized and tested as potential antipsychotics in several in vitro and in vivo assays. The compounds possessed good affinity for D2 receptors, together with a greater affinity for 5-HT2 receptors, a profile which has been proposed as a model for atypical antipsychotics. Several agents also displayed a high potency in the climbing mice assay on oral administration, suggesting a potent antipsychotic effect as compared to reference standards. Compound 23 was selected for further pharmacological evaluation. Induction of catalepsy and inhibition of stereotypies weaker than standards, along with a lower increase in serum prolactin levels, were indicative of a potential atypical profile for this compound. From these results, 7-[3-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)piperidin-1-yl]propoxy]-3-(hydroxymethyl )chromen- 4-one (23, abaperidone) has been proposed for clinical evaluation in humans as a potential atypical antipsychotic.

Subacute toxicity of ebrotidine in rats and dogs.

Subacute toxicity studies of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl] thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) were performed in Spragu-Dawley rats and Beagle dogs. Both animal species were administered with the same dose levels (50, 200 and 500 mg/kg) for 4 and 7 weeks, respectively. In a previous 4-week subacute toxicity study in the rat, ranitidine and cimetidine at 500 mg/kg were used as reference drugs. The results indicated that ebrotidine was well tolerated at 50 mg/kg, while there were dose-related effects at 200 and 500 mg/kg. Probably due to its pharmacokinetics, ebrotidine was more toxic in dogs than in rats, since the most severe effects were the death or sacrifice in extremis of two dogs from the high dose group which had undergone rectal prolapse, while no deaths occurred in the rats. The changes that were very likely related to treatment (500 mg/kg) were a lower weight in both species, a slight decrease of hematocrit and red blood cells in rats, single increments of transaminases, alkaline phosphatase and lactate dehydrogenase in dogs (some animals of the 200 mg/kg dose group were also affected) and a higher liver weight. These effects with a few exceptions were found to be common to cimetidine and ranitidine.

Chronic toxicity of ebrotidine in rats and dogs.

The results obtained in the chronic toxicity studies of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) by oral route in rats and in Beagle dogs are reported. Rats were administered for 6 months and dogs for 12 months. The doses were 50, 200 and 500 mg/kg in rats and 50, 200 and 400 mg/kg in dogs. The dose of 400 mg/kg was reduced to 350 mg/kg after 3 months of treatment, due to its toxicity. The effects probably related to the administration of ebrotidine were as follows: three dogs from the high dose group died after 3, 4.5 and 8 months of treatment (in rat there was no mortality); occult blood in faeces; lower weight gain in the high dose group (in rats only females were affected); lower food consumption in rats from the high dose group (and also females from the middle dose group); reduction of erythrocyte count and packed cell volume, only in rats and at the end of the study; alkaline phosphatases increment in rats and dogs; proteinemia decrease in rats; and a tendency to decrease in the testicular weight, which was not statistically significant (p > 0.05). The only histopathological changes observed were moderate erosions or ulcerations in the intestinal mucosa of some dogs from the high dose group. These effects coincide with those published for other competitive H2-receptor inhibitors. The maximum toxic effect-free level was 50 mg/kg for both rats and dogs, which provides a wide safety margin with respect to the therapeutic dose.

Antiinflammatory activity of topically applied sertaconazole nitrate.

The antiinflammatory activity of topically applied sertaconazole nitrate was investigated. The dermal administration of 2% sertaconazole to rats, in which edema was induced by application of croton oil in the external ear, induced a 39.8% reduction of edema. The results show that sertaconazole applied by topical route at the concentration at which it is used in clinic, has antiinflammatory action in this experimental model.