QuickView for Captopril (compound)

Summary
General Info

PubChem

PubChem Compound 11859209

Name:	Captopril
PubChem Compound ID:	11859209
Description:	A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.
Molecular formula:	C₉H₁₄NO₃S^-
Molecular weight:	216.278 g/mol
Synonyms:	ZINC00057001; 62571-86-2

DrugBank

Identification

Name:	Captopril
Name (isomeric):	DB01197
Drug Type:	small molecule
Description:	A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.
Synonyms:	L-Captopril; Captopryl; Captoprilum [INN-Latin]
Brand:	Hypertil, Captolane, Cesplon, Acepril, Captoril, Lopril, Tenosbon, Hipertil, Lopirin, Acepress, Tensoprel, Alopresin, Capoten, Dilabar, Garranil (discontinued), Apopril
Brand name mixture:	Capozide(captopril + hydrochlorothiazide), Aceplus(captopril + hydrochlorothiazide), Acediur(captopril + hydrochlorothiazide)
Category:	Angiotensin-converting Enzyme Inhibitors, Antihypertensive Agents
CAS number:	62571-86-2

Pharmacology

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.
Pharmacology:	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... show more » 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. show less «
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, w... show more » 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. show less «
Absorption:	60-75% in fasting individuals; food decreases absorption by 25-40% (some evidence indicates that this is not clinically significant)
Protein binding:	25-30% bound to plasma proteins, primarily albumin
Biotransformation:	Hepatic. Major metabolites are captopril-cysteine disulfide and the disulfide dimer of captopril. Metabolites may undergo reversible interconversion.
Half Life:	2 hours
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

Interactions

Food interaction:

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.

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.

Drug interaction:

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.
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.
Lithium	The ACE inhibitor increases serum levels of lithium
Tizanidine	Tizanidine increases the risk of hypotension with the ACE inhibitor
Tobramycin	Increased risk of nephrotoxicity

Targets

Angiotensin-converting enzyme

72 kDa type IV collagenase

Matrix metalloproteinase-9

Enzymes

Cytochrome P450 2D6

Transporters

Multidrug resistance protein 1

Oligopeptide transporter, small intestine isoform

Solute carrier family 22 member 6

Carriers

Serum albumin