Biomaterial Database

Cimetidine and other H2 receptor antagonists as powerful hydroxyl radical scavengers. 1993

T L Ching, and G R Haenen, and A Bast

Faculty of Chemistry, Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands.

Hydroxyl radical scavengers are able to compete with deoxyribose for the hydroxyl radicals generated in a reaction mixture. We found that the H2 receptor antagonists like cimetidine, burimamide, ranitidine, famotidine and tiotidine except for being good inhibitors in histamine-stimulated gastric acid secretion, were also very powerful hydroxyl radical scavengers. Rate constants for reaction of these drugs with hydroxyl radicals ranged from 7.7 x 10(9) Ms-1 to 14.8 x 10(9) M-1 s-1. These rate constants are much higher than for the well-known hydroxyl radical scavenger mannitol (1.7 x 10(9) M-1 s-1). In this study we investigated which part of the cimetidine molecule might be responsible for its potent hydroxyl radical scavenging activity. Testing fragments of the cimetidine molecule revealed that the guanidine moiety of cimetidine had little hydroxyl radical scavenging activity. However the other part of the molecule, the methylated imidazole with a sulfur and amino group containing side chain appeared to be a powerful hydroxyl radical scavenger.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D002927	Cimetidine	A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.	Altramet,Biomet,Biomet400,Cimetidine HCl,Cimetidine Hydrochloride,Eureceptor,Histodil,N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine,SK&F-92334,SKF-92334,Tagamet,HCl, Cimetidine,Hydrochloride, Cimetidine,SK&F 92334,SK&F92334,SKF 92334,SKF92334
D006635	Histamine H2 Antagonists	Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.	Antihistaminics, H2,H2 Receptor Blockader,Histamine H2 Antagonist,Histamine H2 Blocker,Histamine H2 Receptor Antagonist,Histamine H2 Receptor Antagonists,Histamine H2 Receptor Blockader,Histamine H2 Receptor Blockaders,Antagonists, Histamine H2,Blockaders, Histamine H2 Receptor,H2 Receptor Blockaders,Histamine H2 Blockers,Receptor Antagonists, Histamine H2,Receptor Blockaders, H2,Antagonist, Histamine H2,Blockader, H2 Receptor,Blockaders, H2 Receptor,Blocker, Histamine H2,Blockers, Histamine H2,H2 Antagonist, Histamine,H2 Antagonists, Histamine,H2 Antihistaminics,H2 Blocker, Histamine,H2 Blockers, Histamine,Receptor Blockader, H2
D006878	Hydroxides	Inorganic compounds that contain the OH- group.
D016166	Free Radical Scavengers	Substances that eliminate free radicals. Among other effects, they protect PANCREATIC ISLETS against damage by CYTOKINES and prevent myocardial and pulmonary REPERFUSION INJURY.	Free Radical Scavenger,Radical Scavenger, Free,Scavenger, Free Radical,Scavengers, Free Radical
D017665	Hydroxyl Radical	The univalent radical OH. Hydroxyl radical is a potent oxidizing agent.