Captopril
From Proteopedia
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* The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information | * The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information | ||
===Mechanism of Action=== | ===Mechanism of Action=== | ||
| - | + | Crystal structures of ACE1 with bound competitive inhibitors reveal the mechanism of inhibition. Lisinopril binds to the ACE1 binding site in an extended conformation, with its phenyl group oriented toward the active site lid while the lysine chain parallels the zinc binding motif helix. <ref name="Natesh"/> <scene name='Angiotensin-Converting_Enzyme/Lisinopril/1'> Lisinopril makes a number of electrostatic interactions with ACE1 binding site residues and the Zinc Ion</scene>, utilizing His 353, Ala 354 (backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520, Tyr 523 and Glu 162 as well as van der Waals interactions between the phenylpropyl group and Val 518. <ref name="Natesh"/>. Another inhibitor, <scene name='Angiotensin-Converting_Enzyme/Captopril/1'>Captopril, binds in a similar fashion</scene>, forming electrostatic interactions with His 353, Glu 384, Lys 511, His 513 and Tyr 520, along with zinc cation. <scene name='Angiotensin-Converting_Enzyme/Enalalprilat/2'>Enalaprilat, a third competitive inhibitor</scene>, binds via electrostatic interactions with His 353, Ala 354 (Backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520 and Tyr 523 along with the zinc cation. All three inhibitors are very effective and are FDA approved for treatment of Angiotensin II related hypertension and other cardiovascular and renal disorders. <ref>PMID:15236580</ref> | |
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
Revision as of 16:55, 28 November 2010
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Better Known as: Capoten
- Marketed By: Bristol-Myers Squibb
- Major Indication: Hypertension & Congestive Heart Failure
- Drug Class: ACE Inhibitor
- Date of FDA Approval (Patent Expiration): 1981 (1996)
- 2009 Sales: N/A
- Why You Should Care: It was the first Angiotensin-Converting Enzyme Inhibitor. Was one of the earliest successes of Structure-Based drug design.
- The following is a list of Pharmacokinetic Parameters. See: Pharmaceutical Drugs for more information
Mechanism of Action
Crystal structures of ACE1 with bound competitive inhibitors reveal the mechanism of inhibition. Lisinopril binds to the ACE1 binding site in an extended conformation, with its phenyl group oriented toward the active site lid while the lysine chain parallels the zinc binding motif helix. [1] , utilizing His 353, Ala 354 (backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520, Tyr 523 and Glu 162 as well as van der Waals interactions between the phenylpropyl group and Val 518. [1]. Another inhibitor, , forming electrostatic interactions with His 353, Glu 384, Lys 511, His 513 and Tyr 520, along with zinc cation. , binds via electrostatic interactions with His 353, Ala 354 (Backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520 and Tyr 523 along with the zinc cation. All three inhibitors are very effective and are FDA approved for treatment of Angiotensin II related hypertension and other cardiovascular and renal disorders. [2]
Pharmacokinetics
| ACE-Inhibitor Pharmacokinetics Comparison at Equivalent Dosages | |||||
|---|---|---|---|---|---|
| Parameter | Captopril | Lisinopril | Enalapril | Benazepril | |
| Tmax (hr) | |||||
| Cmax (ng/ml) | |||||
| Bioavailability (%) | |||||
| Protein Binding (%) | 96.7 | ||||
| T1/2 (hr) | |||||
| AUC (ng/ml/hr) | |||||
| IC50 (nM) | |||||
| Equivalent Dosage (mg) | |||||
| Metabolism | |||||
