The antihypertensive drug class of angiotensin-converting enzyme (ACE) inhibitors was developed following the discovery and testing of teprotide, a nonapeptide isolated from the venom of a Brazilian pit viper, Bothrops jararaca.1-4 In testing, teprotide was found to be an effective, non-toxic antihypertensive.4,5 The primary activity of teprotide results from blockade of the angiotensin I converting enzyme, the core step in the renin-angiotensin-aldosterone system, which results in reductions in angiotensin II levels.4-6 Because the naturally based teprotide was scarce and required injection, there was limited clinical testing.1,7 In 1974, the first orally active ACE inhibitor captopril was developed and manufactured in a pharmaceutical laboratory.5-8
References
- Cushman DW, Ondetti MA. History of the design of captopril and related inhibitors of angiotensin converting enzyme. Hypertension 1991; 17 (4): 589-592.
- Ferreira SH. A bradykinin‐potentiating factor (BPF) present in the venom of Bothrops jararaca. Br J Pharmacol Chemother 1965; 24: 163-169.
- Ferreira SH, Bartelt DC, Greene LJ. Isolation of bradykinin-potentiating peptides from Bothrops jararaca venom. Biochemistry 1970; 9 (13): 2583-2593.
- Ondetti MA, Williams NJ, Sabo EF, Pluscec J, Weaver ER, Kocy O. Angiotensin-converting enzyme inhibitors from the venom of Bothrops jararaca. Isolation, elucidation of structure, and synthesis. Biochemistry 1971; 10 (22): 4033-4039.
- Antonaccio MJ, Rubin B, Horovitz ZP. Effects of captopril in animal models of hypertension. Clin Exp Hypertens 1980; 2 (3-4): 613-637.
- Petrillo EW, Jr., Ondetti MA. Angiotensin-converting enzyme inhibitors: medicinal chemistry and biological actions. Med Res Rev 1982; 2 (1): 1-41.
- Smith CG, Vane JR. The discovery of captopril. FASEB J 2003; 17 (8): 788-789.
- DiBianco R. Adverse reactions with angiotensin converting enzyme (ACE) inhibitors. Med Toxicol 1986; 1 (2): 122-141.
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