Captopril

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Revision as of 16:58, 28 November 2010

Rosiglitazone, also known as Avandia

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Contents

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 Ramipril Enalapril Benazepril Perindopril Trandolapril
Tmax (hr)
Cmax (ng/ml)
Bioavailability (%)
Protein Binding (%) 96.7
T1/2 (hr)
AUC (ng/ml/hr)
IC50 (nM)
Equivalent Dosage (mg)
Metabolism

References

  1. ↑ 1.0 1.1 Natesh R, Schwager SL, Sturrock ED, Acharya KR. Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. Nature. 2003 Jan 30;421(6922):551-4. Epub 2003 Jan 19. PMID:12540854 doi:http://dx.doi.org/10.1038/nature01370
  2. ↑ Natesh R, Schwager SL, Evans HR, Sturrock ED, Acharya KR. Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry. 2004 Jul 13;43(27):8718-24. PMID:15236580 doi:10.1021/bi049480n

Proteopedia Page Contributors and Editors (what is this?)

David Canner, Alexander Berchansky

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