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H2 Receptor Blockers

H2 receptor antagonists are competitive antagonists that bind to the H2 receptor more strongly than histamine, preventing acid secretion. The document traces the structural evolution of cimetidine from histamine and its analogs to increasingly potent H2 receptor antagonists with improved oral bioavailability and reduced toxicity, culminating in cimetidine. There was a need to develop more potent and long-acting antisecretory agents to treat conditions like nocturnal acidity and avoid acid rebound.

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Apurba Sarker Apu
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389 views11 pages

H2 Receptor Blockers

H2 receptor antagonists are competitive antagonists that bind to the H2 receptor more strongly than histamine, preventing acid secretion. The document traces the structural evolution of cimetidine from histamine and its analogs to increasingly potent H2 receptor antagonists with improved oral bioavailability and reduced toxicity, culminating in cimetidine. There was a need to develop more potent and long-acting antisecretory agents to treat conditions like nocturnal acidity and avoid acid rebound.

Uploaded by

Apurba Sarker Apu
Copyright
© Attribution Non-Commercial (BY-NC)
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd

H2 receptor antagonists

PHRM 304

H2 receptor antagonists
Histamine congeners Be recognized by the receptor Bind more strongly than histamine Not trigger acid secretion Competitive antagonists

Imidazole

Furan

Thiazole

Thiazole

Structural evolution of Cimetidine:

Histamine H1 = H2 agonist

Structural evolution of Cimetidine:

5-Methylhistamine A highly selective H2 agonist (H2>H1)

Structural evolution of Cimetidine:

N-guanylhistamine Weak antagonist Partial H2 receptor agonist Guanidine: Strongly basic group so remain as charged group

Structural evolution of Cimetidine:


2-4

Methyl thiourea Neutral, non-charged

Burimamide Full antagonist Low potency Poor oral bioavailability Toxic (Thiourea)

Structural evolution of Cimetidine:

Electronegative thioether

Metiamide

Full H2 antagonist Higher potency Improved oral bioavailability Toxic: Bone marrow toxicity (Thiourea)

Structural evolution of Cimetidine:

Cimetidine

Full H2 antagonist Higher potency Improved oral bioavailability Low toxicity

The need to develop more potent antisecretory agents:


Acetylcholine and gastrin act on parietal cells to secrete gastric acid May develop tolerance or resistance Short acting: cannot be used in case of nocturnal acidity Acid rebound property.

Downregulation and upregulation


Downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external variable. An increase of a cellular component is called upregulation.

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