Captopril: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
David Canner (talk | contribs)
7,699 edits
No edit summary
David Canner (talk | contribs)
7,699 edits
No edit summary
Line 1: Line 1:
<applet  load="" size="480" color="" frame="true"  spin="on" Scene ="Rosiglitazone/Rosiglitazon/1" align="right" caption="Rosiglitazone, also known as Avandia"/>
<applet  load="" size="480" color="" frame="true"  spin="on" Scene ="Captopril/Captopril/2" align="right" caption="Captopril, also known as Capoten"/>
===Better Known as: Capoten===
===Better Known as: Capoten===
* Marketed By: Bristol-Myers Squibb<br />
* Marketed By: Bristol-Myers Squibb<br />
Line 6: Line 6:
* Date of FDA Approval (Patent Expiration): 1981 (1996)<br />
* Date of FDA Approval (Patent Expiration): 1981 (1996)<br />
* 2009 Sales: N/A
* 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.  
* 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
* 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">PMID:12540854</ref> . 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>
Extensive research has validated a pathological role for Angiotensin II in cardiac, renal and vascular diseases. <ref>PMID:17083068</ref> Bradykinin, a small peptide that counterbalance the effects of Angiotensin II by acting as a strong vasodilator upon binding AT2, is degraded by the same ACE-1 enzyme. Since ACE-1 is the primary producer of Angiotensin II and primary degrader of Bradykinins, inhibition of ACE-1 has proven an effective treatment for Hypertension and Congestive Heart Failure. Captopril binds to the ACE-1 binding site of <scene name='Captopril/Ace/1'>Angiotensin-Converting enzyme</scene>, preventing ACE-1 from binding angiotensin. Captopril,<scene name='Captopril/Captopril_binding/1'> binds ACE-1 precisely</scene>, forming electrostatic interactions with His 353, Glu 384, Lys 511, His 513 and Tyr 520, along with zinc cation. <ref>PMID:15236580</ref>
===Pharmacokinetics===
===Pharmacokinetics===


Retrieved from "https://proteopedia.org/Captopril"