The selective glucocorticoid receptor agonist mapracorat displays a favourable safety-efficacy ratio for the topical treatment of inflammatory skin diseases in dogs.

BACKGROUND: Mapracorat is a nonsteroidal Selective Glucocorticoid Receptor Agonist (SEGRA) that is presumed to have a better therapeutic index compared to classical glucocorticoids. OBJECTIVES: To compare the efficacy and safety of mapracorat with classical glucocorticoids used for the treatment of allergic skin diseases in dogs. ANIMALS: Six laboratory beagles. METHODS: The effect of mapracorat on lipopolysaccharide-induced TNFα secretion from canine peripheral blood derived mononuclear cells (PBMC) was tested. In vivo, mapracorat was compared to triamcinolone acetonide using a skin inflammation model. Skin fold thickness was determined after daily administration of mapracorat and triamcinolone acetonide over 14 days. RESULTS: Mapracorat concentration dependently inhibited TNFα secretion from activated canine PBMC with a half maximal inhibitory concentration (IC50 ) value of approximately 0.2 nmol/L. Intradermal injection of compound 48/80 (50 µg in 50 µL saline) resulted in a clear wheal and flare reaction over the 60 min observation period. Topical pre-treatment with mapracorat (0.1%) and triamcinolone acetonide (0.015%) led to significant reduction in the wheal and flare responses compared to vehicle (acetone) treated areas. However, once daily topical administration of triamcinolone acetonide significantly reduced skin fold thickness from day 8 to 14, whereas no such reduction was observed for mapracorat. CONCLUSION: These results demonstrate that mapracorat has comparable anti-inflammatory efficacy to classical steroidal glucocorticoids under these experimental settings and maintenance of skin fold thickness indicates a better safety profile compared to triamcinolone acetonide at equipotent concentrations. This profile further suggests that SEGRAs show promise in the management of inflammatory and pruritic skin diseases in dogs.

Tolerability and efficacy of the intestinal phosphate binder Lantharenol® in cats.

BACKGROUND: Tolerability and efficacy of the intestinal phosphate binder Lantharenol® (lanthanum carbonate octahydrate) were tested in two prospective, randomized and negative controlled laboratory studies with healthy adult cats fed commercial maintenance diets non-restricted in phosphorus. In the first study, the maximal tolerated dose was determined. Starting from a dose of 0.125 g/kg body weight mixed with the daily feed ration, the dose of Lantharenol® was doubled every other week until signs of intolerability were observed (N=10 cats compared to 5 untreated controls). In the second study, the effects of feed supplementation for two weeks with approximately 2, 6, and 20% of the maximal tolerated dose on phosphorus excretion patterns and balance were assessed (N=8 cats per group). RESULTS: Lantharenol® was found to be safe and well tolerated up to the dose of 1 g/kg bodyweight, corresponding to a concentration of 84 g Lantharenol®/kg complete feed, defined as dry matter with a standard moisture content of 12%. Feed supplementation for two weeks with approximately 2-20% of this dosage (i.e., 1.6, 4.8, and 16 g/kg complete feed) resulted in a shift from urinary to faecal phosphorus excretion. Apparent phosphorus digestibility was dose-dependently reduced compared to the control group fed with diet only (N=8). CONCLUSIONS: The feed additive was well accepted and tolerated by all cats. Therefore, Lantharenol® presents a well tolerated and efficacious option to individually tailor restriction of dietary phosphorus as indicated, for instance, in feline chronic kidney disease.

Effects of acute and repeated administration of a cholinesterase inhibitor on timing behaviour.

It has been hypothesised that a leftward shift in the response distribution obtained in the peak interval (PI) procedure is a characteristic of cognitive enhancement in which mental processes are speeded. Metrifonate, a cholinesterase inhibitor with reported cognitive enhancing properties in many animal models of learning and memory, was tested in the PI procedure. Acute administration of 3 and 60 mg/kg but not 1 and 30 mg/kg in fully trained rats shifted the response distribution to the right, whereas subchronic administration of 10, 30 or 50 mg/kg during task acquisition had no effect on timing behaviour. On the basis of the present data, it can be concluded that the effects of a cognition enhancer in the PI procedure cannot be predicted from the scalar expectancy theory (SET). Furthermore, SET does not appear to be an appropriate tool for analysing the acquisition of timing behaviour.