Drug Development

New drugs are often discovered when the pathophysiology of specific disease process become better understood. The 20th century was marked by progressive improvements in our understanding of the role of hormones, neurotransmitters, receptors and enzymes that are involved in various illnesses.

Important examples include:

• Parkinson's disease. The chance discovery that Parkinsonian features such as impaired movement, rigidity and tremor were caused by depletion of dopamine in the brain and consequent dominance of cholinergic transmission has led to the use of L-dopa, dopa decarboxylase inhibitors, catechol-o-methyltransferase inhibitors and anticholinergic drugs (Fig 3).
• Hypertension. The recognition of the importance of the sympathetic nervous system and renin-angiotensin system (Fig 4) to the vasoconstriction, increased peripheral resistance and sodium retention that characterise many hypertensive states led to the development of beta-adrenoceptor blocking drugs (e.g. atenolol), angiotensin-converting enzyme inhibitors (e.g. enalapril), angiotensin receptor antagonists (e.g. losartan) and renin inhibitors.
• Peptic ulceration. The central role of the H+/K+ exchanger in generating acid from gastric parietal cells, and the fact that this process was stimulated by histamine led to the development of the proton pump inhibitors (e.g. omeprazole) and histamine-2 receptor antagonists (e.g. ranitidine).
• Diabetes. The understanding that type 1 diabetes resulted from a loss of pancreatic insulin production and that type 2 diabetes is caused by both deficient insulin release and reduced sensitivity to the effects of insulin in tissues has been the basis for the use of insulin and the development of numerous other drugs.