Cimetidine

Cimetidine (Food & Drug Administration for prescriptions starting January 1, 1979.

Clinical use

Main article:H2-receptor antagonist

History and development

Cimetidine was the prototypical histamine antagonist to suppress stomach acid secretion.

At the time (1964) it was known that antihistamines had no effect on acid production. In the process, the SK&F scientists also proved the existence of histamine H₂-receptors.

The SK&F team used a rational drug-design structure starting from the structure of histamine - the only design lead, since nothing was known of the then hypothetical H₂-receptor. Hundreds of modified compounds were synthesised in an effort to develop a model of the receptor. The first breakthrough was N^α-guanylhistamine, a partial H₂-receptor antagonist. From this lead the receptor model was further refined and eventually led to the development of competitive antagonist at the H₂-receptor 100-times more potent than N^α-guanylhistamine, proved the existence of the H₂-receptor.

Burimamide was still insufficiently potent for oral administration and further modification of the structure, based on modifying the guanidine-analogues were investigated until the ultimate discovery of cimetidine.

Other uses

There have been two studies relating to the use of Cimetidine for treatment of warts in children. According to the studies, a daily dosage of 400mg of Cimetidine can remove over 200 warts from a 15 year old child.[1]

Another study by Yokoyama et al used Cimetidine for the treatment of Chronic Calcifying Tendonitis of the shoulder. The small scale study took 16 individuals with calcifying tendonitis in one shoulder, all of which had previously attempted other forms of therapy including steroid injection and arthroscopic lavage. During the course of the study 10 patients reported an elimination of pain and 9 displayed a complete disappearance of Calcium deposits. With results being on a small scale, it has been recommended that Cimetidine, for the treatment of chronic calcifying tendonitis of the shoulder, be opened to large scale clinical trials. [2]

Cimetidine has also been reported for use in treatment of colorectal cancer - it is however not approved in the US by the FDA for cancer treatment.

Shortcomings and side effects

Cimetidine is a known inhibitor of many Hydroxychloroquine^{[citation needed]}.

The development of longer-acting H₂-receptor antagonists with reduced adverse effects such as ranitidine proved to be the downfall of cimetidine and, whilst it is still used, it is no longer amongst the more widely used H₂-receptor antagonists. Cimetidine should be used with caution is causes of hepatic impairment and cardiovascular disease^{[citation needed]}. Side effects can include dizziness, and more rarely, headache. BIOAVAILABILITY: The observed bioavailibility of cimetidine is almost 60%.

References

• Michnovicz JJ, Galbraith RA .Cimetidine inhibits catechol estrogen metabolism in women. Metabolism. 1991 Feb;40(2):170-4. PMID 1988774