Molecular mechanisms in therapy of acid-related diseases.
Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration; therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities. Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of a novel class of agents, the acid pump antagonists.
Shin
J M
JM
Department of Physiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Vagin
O
O
Munson
K
K
Kidd
M
M
Modlin
I M
IM
Sachs
G
G
D004415:Dyspepsia / Q000188:drug therapy* / Q000201:enzymology; D005744:Gastric Acid / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000201:enzymology; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000201:enzymology; D054328:Proton Pump Inhibitors / Q000737:chemistry / Q000627:therapeutic use
D054328:Proton Pump Inhibitors; D017506:H(+)-K(+)-Exchanging ATPase