SEARCH FOR AN H2-RECEPTOR HISTAMINE ANTAGONIST
In the beginning of the 20th century, Histamine was discovered. Subsequent studies proved that histamine was the principal mediator of the inflammation and the shock. Antihistamines were used by the pharmacologists to identify various actions of the histamine in the different tissues. Several actions of histamine had been noted that could not be specifically antagonized by these drugs: for example, the stimulation of the gastric acid secretion in rats, cats or dogs; inhibition of rat uterus contractions. Some pointers to the differentiation of histamine receptors had been obtainedby considering the selectivity of action of agonists on these different tissue systems, and the results led Ash and …show more content…
Several configurations of it were formed in the solution due to the rotations of alkyl chain, forms of imidazole ring and the planar configurations of thioureido ring. Replacing side chain –CH2- with –S- result in the formation of Thioburimamide with improved the activity and by adding 4-methyl on the imidazole ring result in the formation of metiamide which also has improved activity but granulocytopenia was reported in the clinical trial patients. Modification of the structure was required to reduce its toxicity and enhance therapeutic H2- receptor antagonist …show more content…
Medicinal chemists replaced-S of metiamide with the isosteric-N and introduced an electron withdrawing –CN (cyano) group to reduce basicity of resulting guanidine. This results in the formation of the compound named cimetidine which resembled in structure with metiamide but do not possess the side effect of granulocytopenia(Ganellin, 2006). Cimetidine (Tagamet)
Personal development reflective log
From the case study of the discovery of Tagamet, I have concluded that the pathway from the lead to the clinical drug is not simple.Figure 2 reflects complex and modular interactions which occur in new drug discovery projects. Failures occur frequently during this process. It is very difficult to predict the accurate duration or the cost of this project.The positive aspect is that it gives one of most challenging and the interesting scientific activities. Drug discovery projects are initiated by belief thatmore efficient new drug will be identified and to make available to the suffering
In the beginning of the 20th century, Histamine was discovered. Subsequent studies proved that histamine was the principal mediator of the inflammation and the shock. Antihistamines were used by the pharmacologists to identify various actions of the histamine in the different tissues. Several actions of histamine had been noted that could not be specifically antagonized by these drugs: for example, the stimulation of the gastric acid secretion in rats, cats or dogs; inhibition of rat uterus contractions. Some pointers to the differentiation of histamine receptors had been obtainedby considering the selectivity of action of agonists on these different tissue systems, and the results led Ash and …show more content…
Several configurations of it were formed in the solution due to the rotations of alkyl chain, forms of imidazole ring and the planar configurations of thioureido ring. Replacing side chain –CH2- with –S- result in the formation of Thioburimamide with improved the activity and by adding 4-methyl on the imidazole ring result in the formation of metiamide which also has improved activity but granulocytopenia was reported in the clinical trial patients. Modification of the structure was required to reduce its toxicity and enhance therapeutic H2- receptor antagonist …show more content…
Medicinal chemists replaced-S of metiamide with the isosteric-N and introduced an electron withdrawing –CN (cyano) group to reduce basicity of resulting guanidine. This results in the formation of the compound named cimetidine which resembled in structure with metiamide but do not possess the side effect of granulocytopenia(Ganellin, 2006). Cimetidine (Tagamet)
Personal development reflective log
From the case study of the discovery of Tagamet, I have concluded that the pathway from the lead to the clinical drug is not simple.Figure 2 reflects complex and modular interactions which occur in new drug discovery projects. Failures occur frequently during this process. It is very difficult to predict the accurate duration or the cost of this project.The positive aspect is that it gives one of most challenging and the interesting scientific activities. Drug discovery projects are initiated by belief thatmore efficient new drug will be identified and to make available to the suffering