Cardiovascular New Drug Discovery The discovery of a new drug results from the combination of both chemical and biological ideas. The

chemical ideas for new cardiovascular drugs come from many different sources ranging from identification of active natural products, through mimicking endogenous mediators, to pure intuition.

Biological ideas may arise from clinical observations and can often be the result of experiments in a completely different field . In the preclinical area, the idea may be to modify clinically definable parameters, (e .g. blood pressure), to modify the physiological control of these parameters, or to modify models of human cardiovascular disease.

The spontaneously hypertensive rat is the best available model of human essential hypertension and it is used to screen all new antihypertensive drugs. Such a standardised testing procedure, however, makes it difficult to find a completely new type of antihypertensive drug. In other areas of cardiovascular disease such as anqina, conqestive heart failure , atherosclerosis and Raynaud's phenomenon there are no reliable preclinical models . Thus, most drugs are designed to treat symptomatically. There is still much to learn about the aetiology of cardiovascular disease and future biological ideas should be aimed at modifying aetiological factors as they are identified.

Chemical and biological ideas are abundant and although information about cardiovascular disease may be incomplete, the clue to discovering new drugs at present lies in using what is known to develop a rational approach for preclinical testing . In this way efficacy, mechanism of action and safety may be determined and it may also be possible to isolate a new approach from existing approaches.

Not only must the new drug be effective, well tolerated and safe, but there must also be a need for it in a particular disease. The market place for drugs is rapidly changing and should be closely monitored, as should the regulatory climate. A new drug should be an improvement on existing drugs and thus , with each new drug, the set of criteria will be higher and the number of clinical and preclinical tests will be greater, leading to higher costs.

At present there is a rapid r-ate of advancement in knowledge of science and technology and this is reflected in the diversity of approaches now available to new drug development.

Computers are also helping to extend our knowledge of physiology. Advances in the field of biology will lead to advances in the field of pharmacology, thus leading to new drugs in the future. Smith. RD. : Drug Development Research 4: 237 (No 3, 1984)

0156-2703/ 84/ 1013-0003/ 0$01.00/ 0 © ADIS Press INPHARMA® 13 Oct 1984 3