Ranitidine (Zantac)

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RANITIDINE

Siddharth Shah

Brand Name: Zantac (GlaxoSmithKline, Prescription); Zantac OTC (Boehringer

Ingelheim, OTC)

Chemical Name: N [2-[[[5-[(dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl]-N'-

methyl-2-nitro-1,1-ethenediamine, HCl.

Structure:

Appearance: White to pale yellow, slightly bitter and a sulfur-like odor.

Primary Use: Relieves ‘heartburn’ associated with acid indigestion and sour

stomach.

How Heartburn occurs: Cells called parietal cells are responsible for acid secretion

in the stomach. If the sphincter of the stomach opens when it should not, to allow

stomach juices to enter the esophagus, heartburn occurs.

Shown above (right) are the parietal cells, the apical membrane being common

between these cells and the stomach lumen. As seen, water and CO2 are converted

to carbonate ion (HCO3-) and a hydrogen ion (H+) by carbonic anhydrase. The HCO3-

is exchanged at the basolateral membrane for a chloride ion by the Cl-/HCO3-

antiporter. This Cl- continues to the apical membrane and by virtue of its



concentration gradient, diffuses into the stomach lumen. The H+, on the other hand,

is exchanged for a potassium ion (K +) expending ATP by the H+/K + ATPase at the

apical membrane. H+ thus enters the stomach lumen. This H+ and the Cl- constitute

the HCl in the stomach. The H+/K + ATPase is, however, not present at the apical

membrane surface at all times. It is transported to the apical membrane only after

histamine activation.

Parietal cells bear receptors for three stimulators of acid secretion, reflecting

neural, paracrine and endocrine control:

Acetylcholine

Gastrin

Histamine (H2 type receptor) – primary modulator.

The H2 receptor is a rhodopsin-like GPCR. Binding of histamine and activation of

the H2 receptor leads to activation of adenylate cyclase (AC). AC catalyzes the

conversion of ATP to cAMP. Elevated cAMP levels activate Protein Kinase A (PKA).PKA phosphorylates certain cytoskeletal proteins involved in transport of the H+/K +

ATPase to the apical membrane.

Mechanism of Action: Ranitidine is a H2 receptor antagonist. It competes with

histamine to bind reversibly to the H2 receptor. By preventing activation of the H2

receptor and the subsequent activation of PKA, ranitidine prevents transport of the

H+/K + ATPase to the apical membrane. Thus, stomach acidification is prevented.

Since the acids are no longer produced, none can enter the esophagus to cause

irritation. Thus, heartburn is prevented.

Ranitidine is found to provide relief from heartburn within 24 hours.



References:

Bowen, R. "The Parietal Cell: Mechanism of Acid Secretion." 20 March 2010.

Biomedical Hypertextbooks: Colorado State University Web Site. 15 April 2010

<http://www.vivo.colostate.edu/hbooks/pathphys/digestion/stomach/parietal.html

>. GlaxoSmithKline. "Prescription Medicines: Zantac." 1 September 2009.

GlaxoSmithKline Web Site. 15 Apil 2010

<http://www.gsk.com/products/prescription-medicines/zantac.htm>.

"IPR000503 Histamine H2 receptor." EMBL-EBI Web Site. 15 April 2010

<http://www.ebi.ac.uk/interpro/IEntry?ac=IPR000503>.

Lodish, et al. Molecular Cell Biology. 6th. New York: W. H. Freeman and

Company, 2007.

"What happens when you have GERD?" 2007. eMED TV Web Site. 15 April 2010

<http://gerd.emedtv.com/gerd-video/what-happens-when-you-have-gerd-video.html>.

"Why Choose Zantac." Zantac OTC Web Site. 15 April 2010

<http://www.zantacotc.com/why/index.jsp>.

"Zantac." 13 April 2009. RxList Web Site. 15 April 2010

<http://www.rxlist.com/zantac-drug.htm>.

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Ranitidine (Zantac)