Benzimidazoles specific agents

Sachs and his colleagues had begun work that would show that H+/K+-ATPase, as the proton pump, moves acid across the membranes of gastric parietal cells (Blum et al, 1971). Scientists at the Swedish firm had focused on imidazoles and specifically, benzimidazoles, apparently in part because cimetidine (like histamine) is an imidazole. By adding a benzimidazole moiety to pyridine-2-thioacetamide, a known antisecretory agent, a new class of substituted benzimidazoles, which would later yield omeprazole was created (Fellenius, 1981). These congeners were sufficiently novel so that patent approval, a necessary component of the project, was likely if the compounds proved useful. 

Inhibitors of a heart-specific subtype (type III) phosphodiesterase, which are positive inotropics, may be used in the short-term treatment of severe congestive cardiac failure, e.g. amrinone, enoximone and milrinone. However, developments of oral formulations of drugs of this type have been halted by the results of the PROMISE trial (Prospective Randomised Milrinone Survival Evaluation trial) which documented a paradoxical increase in mortality in class IV heart failure patients randomised to receive milrinone. However, some benzimidazole derivatives with class III phosphodiesterase inhibitor actions seem to be beneficial in heart failure. The agent vesnarinone is an orally active compound that may act as a class III phosphodiesterase inhibitor but appears to be a vasodilator with multiple mechanisms. See HEART FAUURE TREATMENT INOTROPIC AGENTS. 

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