Acepress (Bernofarm (Indonesia), BMS (Italy));Acepril (BMS (United Kingdom));Alopresin;Apopril;Capoten (Bristol-Myers Squibb, Par);Captolane (Sanofi-Aventis (France));Captoril (Novopharm (Canada));Cesplon (Esteve (Spain));Dilabar (Qualigen (Spain));Garranil (discontinued) (Aristegui (Spain));Hipertil (Normal (Portugal));Hypertil (Normal (Portugal));Lopirin (BMS (Germany,Switzerland));Lopril (Orion (Finland), BMS (France));Tenosbon;Tensoprel (Rubio (Spain));

Captoprilum [INN-Latin];Captopryl;L-Captopril;

Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Captopril may be used in the treatment of hypertension.

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Synthesis Reference

Not Available

General Reference

Atkinson AB, Robertson JI: Captopril in the treatment of clinical hypertension and cardiac failure. Lancet. 1979 Oct 20;2(8147):836-9. Pubmed Patchett AA, Harris E, Tristram EW, Wyvratt MJ, Wu MT, Taub D, Peterson ER, Ikeler TJ, ten Broeke J, Payne LG, Ondeyka DL, Thorsett ED, Greenlee WJ, Lohr NS, Hoffsommer RD, Joshua H, Ruyle WV, Rothrock JW, Aster SD, Maycock AL, Robinson FM, Hirschmann R, Sweet CS, Ulm EH, Gross DM, Vassil TC, Stone CA: A new class of angiotensin-converting enzyme inhibitors. Nature. 1980 Nov 20;288(5788):280-3. Pubmed Smith CG, Vane JR: The discovery of captopril. FASEB J. 2003 May;17(8):788-9. Pubmed

Type	small molecule

Classes

Not Available

Substructures

Not Available

ANTIHYPERTENSIVES 降血压;

Indication	For the treatment of essential or renovascular hypertension (usually administered with other drugs, particularly thiazide diuretics). May be used to treat congestive heart failure in combination with other drugs (e.g. cardiac glycosides, diuretics, β-adrenergic blockers). May improve survival in patients with left ventricular dysfunction following myocardial infarction. May be used to treat nephropathy, including diabetic nephropathy.
Pharmacodynamics	Captopril, an ACE inhibitor, antagonizes the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain its effects by causing increased vasodilation and decreased blood pressure.
Mechanism of action	There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Captopril, one of the few ACE inhibitors that is not a prodrug, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Captopril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. Captopril’s affinity for ACE is approximately 30,000 times greater than that of ATI.
Absorption	60-75% in fasting individuals; food decreases absorption by 25-40% (some evidence indicates that this is not clinically significant)
Volume of distribution	Not Available
Protein binding	25-30% bound to plasma proteins, primarily albumin
Metabolism	Hepatic. Major metabolites are captopril-cysteine disulfide and the disulfide dimer of captopril. Metabolites may undergo reversible interconversion. Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us. Substrate Enzymes Product Captopril captopril-cysteine disulfide Details
Route of elimination	Not Available
Half life	2 hours
Clearance	Not Available
Toxicity	Symptoms of overdose include emesis and decreased blood pressure. Side effects include dose-dependent rash (usually maculopapular), taste alterations, hypotension, gastric irritation, cough, and angioedema.
Affected organisms	Humans and other mammals
Pathways	Pathway Name SMPDB ID Captopril Pathway SMP00146

Properties
State	solid
Experimental Properties	Property Value Source melting point 106 °C PhysProp water solubility Freely soluble Not Available logP 0.34 RANADIVE,SA ET AL. (1992)
Predicted Properties	Property Value Source water solubility 4.52e+00 g/l ALOGPS logP 1.02 ALOGPS logP 0.73 ChemAxon logS -1.7 ALOGPS pKa (strongest acidic) 4.02 ChemAxon pKa (strongest basic) -1.2 ChemAxon physiological charge -1 ChemAxon hydrogen acceptor count 3 ChemAxon hydrogen donor count 2 ChemAxon polar surface area 57.61 ChemAxon rotatable bond count 3 ChemAxon refractivity 54.63 ChemAxon polarizability 21.72 ChemAxon

Drug	Interaction
Amiloride	Increased risk of hyperkalemia
Aprotinin	In study of nine patients with untreated hypertension, aprotinin infused intravenously in a dose of 2 million KIU over two hours blocked the acute hypotensive effect of 100mg of captopril.
Azilsartan medoxomil	Pharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
Drospirenone	Increased risk of hyperkalemia
Icatibant	Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Lithium	The ACE inhibitor increases serum levels of lithium
Potassium	Increased risk of hyperkalemia
Spironolactone	Increased risk of hyperkalemia
Terbinafine	Terbinafine may reduce the metabolism and clearance of Captopril. Consider alternate therapy or monitor for therapeutic/adverse effects of Captopril if Terbinafine is initiated, discontinued or dose changed.
Tizanidine	Tizanidine increases the risk of hypotension with the ACE inhibitor
Tobramycin	Increased risk of nephrotoxicity
Treprostinil	Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Triamterene	Increased risk of hyperkalemia

• Captopril decreases the excretion of potassium. Salt substitutes containing potassium increase the risk of hyperkalemia.
• Food decreases absorption by 25 - 40%. Clinical significance is debatable.
• Herbs that may attenuate the antihypertensive effect of captopril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
• High salt intake may attenuate the antihypertensive effect of captopril.