Laboratorios Salvat SA

Background and purpose: Highly selective M3muscarinic receptor antagonists may represent a better treatment for overactive bladder syndrome, diminishing side effects. Cardiac side effects of non‐selective antimuscarinics have been associated with activity at M2receptors as these receptors are mainly responsible for muscarinic receptor‐dependent bradycardia. We have investigated a novel antimuscarinic, SVT‐40776, highly selective for M3over M2receptors (Ki = 0.19 nmol·L−1for M3receptor affinity). This study reports the functional activity of SVT‐40776 in the bladder, relative to its activity in atria.Experimental approach: In vitroandex vivo(oral dosing) inhibition of mouse detrusor and atrial contractile responses to carbachol were used to study the functional activity of SVT‐40776. Thein vivoefficacy of SVT‐40776 was characterized by suppression of isovolumetric spontaneous bladder contractions in anaesthetized guinea pigs after intravenous administration.Key results: SVT‐40776 was the most potent in inhibiting carbachol‐induced bladder contractions of the anti‐cholinergic agents tested, without affecting atrial contractions over the same range of concentrations. SVT‐40776 exhibited the highest urinary versus cardiac selectivity (199‐fold). In the guinea pigin vivomodel, SVT‐40776 inhibited 25% of spontaneous bladder contractions at a very low dose (6.97 µg·kg−1i.v), without affecting arterial blood pressure.Conclusions and implications: SVT‐40776 is a potent inhibitor of M3receptor‐related detrusor contractile activity. The absence of effects on isolated atria preparations represents an interesting characteristic and suggests that SVT‐40776 may lack unwanted cardiac effects; a feature especially relevant in a compound intended to treat mainly elderly patients.British Journal of Pharmacology(2009) doi:10.1111/j.1476‐5381.2008.00082.x

The antifungal activity of eberconazole, a new imidazole derivative, against 124 clinical isolates of Candida comprising eight different species and to 34 isolates of Cryptococcus neoformans was compared to those of clotrimazole and ketoconazole. MICs of eberconazole, determined by the National Committee for Clinical Laboratory Standards standardized microbroth method, were equal to or lower than those of other azoles, especially for Candida krusei and Candida glabrata , which are usually resistant to triazoles.

The cornea is a very particular tissue due to its transparency and its barrier function as it has to resist against the daily insults of the external environment. In addition, maintenance of this barrier function is of crucial importance to ensure a correct corneal homeostasis. Here, the corneal epithelial permeability has been assessed in vivo by means of non-invasive tetrapolar impedance measurements, taking advantage of the huge impact of the ion fluxes in the passive electrical properties of living tissues. This has been possible by using a flexible sensor based in SU-8 photoresist. In this work, a further analysis focused on the validation of the presented sensor is performed by monitoring the healing process of corneas that were previously wounded. The obtained impedance measurements have been compared with the damaged area observed in corneal fluorescein staining images. The successful results confirm the feasibility of this novel method, as it represents a more sensitive in vivo and non-invasive test to assess low alterations of the epithelial permeability. Then, it could be used as an excellent complement to the fluorescein staining image evaluation.