ABSTRACT

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The benzamides and nicotinamides represent a class of drugs that have experienced an unusually broad spectrum for clinical development. So far, these agents are being or have already been developed as clinically relevant antipyschotic (sulpiride), antiemetic (metoclopramide), antiarrhythmic (lidocaine), diabetic (nicotinamide), local anesthetic (procainamide), chemosensitizing/antitumor (declopramide), multidrug resistance reversing and anti-inflammatory drugs.1 This diverse clinical spectrum is paralleled by an equally diverse mode of action profile which includes effects on tumor microcirculation, DNA repair, poly(ADP-ribose) polymerase (PARP), dopamine/hydroxytryptamine receptors, ADP-ribosyl cyclase/Ca homeostasis, apoptosis, NF-κB, P-glycoprotein, and phosphodiesterases (see patents described below). This is an unusual situation for drug development where small informational molecules such as benzamides and nicotinamides could influence so many seemingly unrelated biological processes. To appreciate further this drug discovery area, it is important to understand that nicotinamide is a vitamin not efficiently manufactured by the body, and hence dietary intake is essential to support human health in a disease-free state.