NELTENEXINE - MORPHOLOGICAL INVESTIGATION OF PROTECTION AGAINST ELASTASE-INDUCED EMPHYSEMA IN RATS

The instillation of elastase into airways is a widely adopted experime ntal method to quickly produce emphysematous lesions that mimic human disease anatomically and physiologically. Experiments were undertaken to determine whether or not neltenexine, a new drug active on surfacta nt production, would diminish the severity of this disease. Anaestheti zed rats were instilled tracheally with porcine pancreatic elastase (4 6 U/mg) dissolved in saline, in a single instillation of 0.33 mg/100 I B. Neltenexine was administered in one experiment at the dose of 25 mg /kg i.p. daily for 30 days. In a second test, neltenexine was given al the same dose six days before the elastase instillation and then by t he same schedule as in the first experiment, this was done in search o f a possible preventive action. At the end of the treatment, lungs wer e removed and fixed and slices were dehydrated, critically point dried , coated with gold and observed by scanning electron microscopy (SEM). Rats that were both pretreated and treated with neltenexine showed a significant reduction in the alveolar deformation induced by elastase. There were no differences between pretreated and treated animals. The se experimental findings suggest that neltenexine might prove to be us eful for preventing pulmonary emphysema. Biochemical studies in man ar e needed to confirm the clinical application of neltenexine.