INHIBITORY EFFECTS OF -HALOALKYLAMINES ON THE RENAL TRANSPORT OF N-METHYLNICOTINAMIDE

¹ Department of Pharmacology, State University of New York, Upstate Medical Center, Syracuse, New York

The specificity and irreversibility of the inhibitory effects of Dibenamine and Dibenzyline for the renal transport of N-methylnicotinamide (NMN) were demonstrated both in vitro and in vivo. These compounds produced a marked reduction (80-90%) in the uptake of NMN in dog renal cortex slices without reducing the uptake of p-aminohippurate. Both compounds inhibited the uptake of NMN in renal cortex slices from dogs pretreated with Dibenamine and Dibenzyline. Slices incubated in these agents and then washed repeatedly were unable to take up NMN, and the extent of inhibition was comparable to that in unwashed slices. Neither agent was able to inhibit the renal tubular secretion of NMN in normal dogs; however, both agents inhibited the secretion of NMN in animals producing an alkaline urine (due to sodium bicarbonate and acetazolamide treatment). The secretion of p-aminohippurate was unaffected in all animals studied. The lack of effect in normal animals may have been due to insufficient binding of the inhibitor in the kidney. The fact that Dibenamine and Dibenzyline are firmly bound in the kidney and are specific inhibitors of NMN transport makes them valuable tools for studying transport sites for organic bases.