This MedLibrary.org supplementary page on Metiamide is provided directly from the open source Wikipedia as a service to our readers. Please see the note below on authorship of this content, as well as the Wikipedia usage guidelines. To search for other content from our encyclopedia supplement, please use the form below:
Related Sponsors
| Metiamide | |
|---|---|
 |
|
| Properties | |
| Molecular formula | C9H16N4S2 |
| Molar mass | 244.38 g mol−1 |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references |
|
Metiamide is an H2-receptor antagonist developed from another H2 antagonist, burimamide.
It was an intermediate compound in the development of the successful anti-ulcer drug cimetidine (Tagamet).
Development of metiamide from burimamide
After discovering that burimamide is largely inactive at physiological pH, due to the presence of its electron donating side chain, the following steps were undertaken to stabilse burimamide:
- addition of a sulfide group close to the imidazole ring, giving thiaburimamide
- addition of methyl group to the 4- position on the imidazole ring to favour the tautomer of thiaburimamide which binds better to the H2-receptor
Metiamide
- is 10 times more potent than burimamide
- inhibited histamine-stimulated release of gastric acid
- increased healing rate of peptic ulcers
- provided symptomatic relief for ulcerous patients.
However,
- in clinical trials, an unacceptable number of patients dosed with metiamide developed agranulocytosis (decreased white blood cell count)
- clinical trials aborted, as patients were left susceptible to infection
Modification of metiamide to cimetidine
It was determined that the thiourea group was the cause of the agranulocytosis. Therefore replacement of the =S in the thiourea group was suggested:
- with =O or =NH resulted in a compound with much less activity (20 times less than metiamide)
- however, the NH form (the guanidine analogue of metiamide) did not show agonistic effects
- to prevent the guanidine group being protonated at physiological pH, electron-withdrawing groups were added
- adding a -C≡N or -NO2 group prevented the guanidine group being protonated and did not cause agranulocytosis
The nitro and cyano groups are sufficiently electronegative to reduce the pKa of the neighbouring nitrogens to the same acidity of the thiourea group, hence preserving the activity of the drug in a physiological environment.
- the -C≡N group (part of a cyanoguanidine moiety) was a little more effective
- it was developed and marketed as cimetidine,
References
 |
The references used in this article may be clearer with a different or consistent style of citation, footnoting, or external linking. This article has been tagged since September 2007. |
- Clayden, J. Greeves, N. Warren, S. Wothers, P. (2001). Organic Chemistry. Oxford. ISBN 0-19-850346-6
 |
This pharmacology-related article is a stub. You can help Wikipedia by expanding it. |
Wikipedia content modification information:
- This page was last modified on 25 April 2008, at 02:01.
Wikipedia Authorship and Review
Wikipedia content provided here is not reviewed directly by MedLibrary.org. Wikipedia content is authored by an open community of volunteers and is not produced by or in any way affiliated with MedLibrary.org.
Wikipedia Usage Guidelines
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article on "Metiamide".
The URL for this specific entry is:
All Wikipedia text is available under the terms of the GNU Free Documentation License. (See Copyrights for details). Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc.