Cimetidine

2-cyano- 1-methyl -3-[ 2 - (5- methylimidazol -4- ylmethylsulfanyl ) ethyl ] guanidine (IUPAC)

• 51481-61-9
• 70059-30-2 (hydrochloride)

A02BA01

Antiallergic agent, gastric acid blocker, an immune stimulant

H2-receptor antagonist

6.8

Slightly soluble in water ( 9.38 g · l-1 at 25 ° C)

Risk

2550 mg · kg -1 ( LD50, mouse, oral)

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Cimetidine is a drug which is used as the H2 - antihistamine for damping the gastric juice. Chemically the substance belongs to the drug class of guanidine derivatives.

Development

Cimetidine is the first introduced into the treatment of heartburn and peptic ulcers H2 antagonist. He was from the mid-1960s by Smith Kline and French (now GlaxoSmithKline), developed in 1976 as Tagamet and came on the market. Tagamet was one of the first blockbuster in the pharmaceutical market.

Pharmacology

Mechanism of action

Cimetidine is a competitive, reversible H2 antagonist of the parietal cells of the gastric mucosa. Thereby, it reduces the gastric acid secretion and the release of the digestive enzyme pepsin, but does not affect the formation of the gastric mucus and gastric emptying. In addition, the vagus and gastrin - induced acid release is still nichtkompetetiv suppressed.

Moreover, cimetidine inhibits H2 receptors on T- suppressor cells and inhibits the effect, resulting in an indirect immunostimulant. It also reduces the secretion of parathyroid hormone and androgens.

Distribution in the body

Cimetidine is administered orally or parenterally and about 70% absorbed in the intestine, especially in the ileum. It is distributed in the bloodstream and also gets into the milk and crosses the placenta. It is metabolized in the liver, excreted in part unchanged in the urine. The half-life is about one hour.

Areas of application

• Ulcers in the stomach, abomasum and duodenum
• Acute pancreatitis and exocrine pancreatic insufficiency
• Gastritis
• Esophagitis and gastroesophageal reflux
• Duodenal - gastric reflux
• Bleeding in the upper gastrointestinal tract
• Gastrinomas and systemic mastocytosis
• Immune stimulation, application eg with melanoma in the horse

Contraindications and side effects

In case of hypersensitivity and severe kidney or liver disease, the administration is contraindicated. The use in food-producing animals is not allowed.

In humans, mental confusion, headaches, gynecomastia, decreased libido, cardiac arrhythmias ( bradycardia) and rarely agranulocytosis were observed. In addition, it has a high delirium inducing potency. In veterinary medicine, there are no reports of side effects.

Interactions

As cimetidine has an inhibitory effect on a few cytochrome P450 enzymes, many interactions are by active extension and amplification possible, thus leading to an incompatibility with drugs which act as enzyme inducers of CYP 450 enzymes, or degraded by selfsame be. This is also a reason why cimetidine is not available in non-prescription OTC sales, compared to the other H2 blockers such as ranitidine and famotidine. Furthermore, cimetidine is therefore no longer recommended therapy of choice, there stands with ranitidine ( and with proton pump inhibitors ) with respect to inhibition of gastric acid, a longer and more effective drug with better tolerability available.

Cimetidine inhibits creatinine secretion in the kidneys and can therefore biochemically a decreased glomerular filtration rate fake. The reason for this is essentially that cimetidine efflux from the proximal tubular cells via the two SLC transporter MATE1 ( SLC47A1, multidrug and toxin extrusion 1) and MATE2 -K ( SLC47A2, multidrug and toxin extrusion 2 - kidney) at the apical side inhibited. In addition, cimetidine inhibited - but somewhat weaker than MATE1 and MATE2 -K - also the organic cation transporter 2 ( OCT2 ) to the basolateral side.

Trade names

Cimetag (A), CimLich (D ), H 2 blockers ( D), Neutromed (A), Ulcostad (A) and more generic (D, A)