Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production.

[1][10][11] With the development of proton pump inhibitors, such as omeprazole, approved for the same indications, cimetidine is available as an over-the-counter formulation to prevent heartburn or acid indigestion, along with the other H2-receptor antagonists.

[4] Reported side effects of cimetidine include diarrhea, rashes, dizziness, fatigue, constipation, and muscle pain, all of which are usually mild and transient.

Examples of specific interactions include, but are not limited to, the following: The mechanism of action of cimetidine as an antacid is as a histamine H2 receptor antagonist.

[25] It reversibly inhibits CYP enzymes by binding directly with the complexed heme-iron of the active site via one of its imidazole ring nitrogen atoms, thereby blocking the oxidation of other drugs.

[52] At typical therapeutic levels, cimetidine has either no effect on or causes small increases in circulating testosterone concentrations in men.

[45] Any increases in testosterone levels with cimetidine have been attributed to the loss of negative feedback on the HPG axis that results due to AR antagonism.

[45][46] At typical clinical dosages, such as those used to treat peptic ulcer disease, the incidence of gynecomastia (breast development) with cimetidine is very low at less than 1%.

[53] In one small study, a 20% incidence of gynecomastia was observed in 25 male patients with duodenal ulcers who were treated with 1,600 mg/day cimetidine.

[52] People taking a dosage of cimetidine of greater than or equal to 1,000 mg showed more than 40 times the risk of gynecomastia than non-users.

[46][45][52] In accordance with the very weak nature of its AR antagonistic activity, cimetidine has shown minimal effectiveness in the treatment of androgen-dependent conditions such as acne, hirsutism (excessive hair growth), and hyperandrogenism (high androgen levels) in women.

Cimetidine was the culmination of a project at Smith, Kline and French (SK&F) Laboratories in Welwyn Garden City (now part of GlaxoSmithKline) by James W. Black, C. Robin Ganellin, and others to develop a histamine receptor antagonist to suppress stomach acid secretion.

Burimamide was still insufficiently potent for oral administration, and further modification of the structure, based on modifying the pKa of the compound, led to the development of metiamide.

[58] The toxicity was proposed to arise from the thiourea group, and similar guanidine analogues were investigated until the ultimate discovery of cimetidine.

In November 1997, the American Chemical Society and the Royal Society of Chemistry in the U.K. jointly recognized the work as a milestone in drug discovery by designating it an International Historic Chemical Landmark during a ceremony at SmithKline Beecham's New Frontiers Science Park research facilities in Harlow, England.

[citation needed] Tagamet has been largely replaced by proton pump inhibitors for treating peptic ulcers, but is available as an over-the-counter medicine for heartburn in many countries.

[63] Cimetidine inhibits ALA synthase activity and hence may have some therapeutic value in preventing and treating acute porphyria attacks.