[Fifty years history of new drugs in Japan: the developments and trends of antihypertensive drugs].

The novel antihypertensive drugs which have been discovered and developed in the latter half of the 20th century were investigated. Newly discovered or improved drugs are approved by the Ministry of Health and Welfare in Japan, and after then they become available for clinical use. We can follow the progress and trends of various new antihypertensive drugs by recording their years of approval. The four primary useful drugs for the treatment of hypertension were developed were introduced as listed in the following: 1. Antihypertensive diuretics: Thiazide and dihydrothiazide were first approved in 1958, and various related drugs including aldosterone antagonists and loop diuretics followed. 2. beta-Adrenergic-blocking drugs: Propranolol was approved in 1966 for heart diseases and for hypertension in 1970. Thereafter many related drugs were developed. 3. Calcium channel-blocking drugs: Nifedipine was approved, for heart disease in 1974 and for hypertension in 1981, and then many related drugs appeared. 4. Angiotensin-converting enzyme inhibitors: Captopril was approved in 1982 and thereafter various related drugs followed. The four categories of these drugs were selected as first choice drugs for the treatment of hypertension in 1988. The development of these excellent useful drugs affected the mortality rates of cerebrovascular diseases (e.g., apoplexy). The mortality curve reaches plateaued in 1963, peaked in 1965, and then declined rapidly. Antihypertensive diuretic drugs stop the rise of mortality, and beta-blocking drugs, Ca-antagonists and ACE-inhibitors promote rapid downward tendency.