Pharmacological properties of FPL 63547, a novel inhibitor of angiotensin‐converting enzyme
1 FPL 63547, in its active diacid form, was a potent inhibitor of rabbit lung angiotensin converting enzyme (ACE) in vitro (IC50 0.51 nm). 2 In conscious normotensive dogs, FPL 63547 (10–300 μg kg−1 i.v.) produced prolonged, dose‐related inhibition of plasma ACE activity and angiotensin I pressor re...
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description | 1
FPL 63547, in its active diacid form, was a potent inhibitor of rabbit lung angiotensin converting enzyme (ACE) in vitro (IC50 0.51 nm).
2
In conscious normotensive dogs, FPL 63547 (10–300 μg kg−1 i.v.) produced prolonged, dose‐related inhibition of plasma ACE activity and angiotensin I pressor responses, without affecting basal blood pressure, heart rate or pressor responses to angiotensin II.
3
In anaesthetized dogs, FPL 63547 diacid (3–300 μg kg−1 i.v. cumulatively) produced dose‐related increases in cardiac output accompanied by falls in total peripheral resistance indicative of vasodilatation. Mild stimulation of cardiac rate and contractility was also observed. Enalapril diacid had a similar profile.
4
FPL 63547 was a highly effective antihypertensive agent after oral administration to spontaneously hypertensive rats (SHR) pretreated with a diuretic. It lowered systolic blood pressure (SBP) on acute administration over the range 3 × 10−7–10−5 mol kg−1 p.o. (⋍ 0.13–4.5 mg kg−1 p.o.). FPL 63547 was more potent than other ACE inhibitors tested, threshold active doses for lisinopril, enalapril and captopril being 10−6, 10−6 and 3 × 10−5 mol kg−1 p.o., respectively. The antihypertensive effects of FPL 63547, unlike those of enalapril and captopril, were of long duration.
5
The antihypertensive efficacy of FPL 63547 was also observed following chronic oral administration. A dose of 0.5 mg kg−1 day−1 once daily for 23 days produced a sustained reduction of SBP. By the end of the treatment period, SBP was significantly lowered both pre‐ and post‐dose, i.e. effective 24 h control had been achieved.
6
The profile of FPL 63547 is consistent with it being a potent, selective and long‐acting ACE inhibitor. As an antihypertensive agent in SHR it compared favourably with other members of this class with respect to potency and duration of action. |
doi_str_mv | 10.1111/j.1476-5381.1990.tb12056.x |
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FPL 63547, in its active diacid form, was a potent inhibitor of rabbit lung angiotensin converting enzyme (ACE) in vitro (IC50 0.51 nm).
2
In conscious normotensive dogs, FPL 63547 (10–300 μg kg−1 i.v.) produced prolonged, dose‐related inhibition of plasma ACE activity and angiotensin I pressor responses, without affecting basal blood pressure, heart rate or pressor responses to angiotensin II.
3
In anaesthetized dogs, FPL 63547 diacid (3–300 μg kg−1 i.v. cumulatively) produced dose‐related increases in cardiac output accompanied by falls in total peripheral resistance indicative of vasodilatation. Mild stimulation of cardiac rate and contractility was also observed. Enalapril diacid had a similar profile.
4
FPL 63547 was a highly effective antihypertensive agent after oral administration to spontaneously hypertensive rats (SHR) pretreated with a diuretic. It lowered systolic blood pressure (SBP) on acute administration over the range 3 × 10−7–10−5 mol kg−1 p.o. (⋍ 0.13–4.5 mg kg−1 p.o.). FPL 63547 was more potent than other ACE inhibitors tested, threshold active doses for lisinopril, enalapril and captopril being 10−6, 10−6 and 3 × 10−5 mol kg−1 p.o., respectively. The antihypertensive effects of FPL 63547, unlike those of enalapril and captopril, were of long duration.
5
The antihypertensive efficacy of FPL 63547 was also observed following chronic oral administration. A dose of 0.5 mg kg−1 day−1 once daily for 23 days produced a sustained reduction of SBP. By the end of the treatment period, SBP was significantly lowered both pre‐ and post‐dose, i.e. effective 24 h control had been achieved.
6
The profile of FPL 63547 is consistent with it being a potent, selective and long‐acting ACE inhibitor. As an antihypertensive agent in SHR it compared favourably with other members of this class with respect to potency and duration of action.</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/j.1476-5381.1990.tb12056.x</identifier><identifier>PMID: 2164863</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Angiotensin I - pharmacology ; Angiotensin-Converting Enzyme Inhibitors - pharmacology ; Animals ; Antihypertensive agents ; Biological and medical sciences ; Blood Pressure - drug effects ; Cardiac Output - drug effects ; Cardiovascular system ; Dogs ; Dose-Response Relationship, Drug ; Heart Rate - drug effects ; Lung - drug effects ; Lung - enzymology ; Male ; Medical sciences ; Peptidyl-Dipeptidase A - blood ; Pharmacology. Drug treatments ; Rabbits ; Rats ; Rats, Inbred SHR ; Thiadiazoles - pharmacology ; Vasodilation - drug effects</subject><ispartof>British journal of pharmacology, 1990-05, Vol.100 (1), p.83-89</ispartof><rights>1990 British Pharmacological Society</rights><rights>1990 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5386-2bf6b381c39a805000248db1fcdc51433c77fc887b648ee0d142e7e5db672cdc3</citedby><cites>FETCH-LOGICAL-c5386-2bf6b381c39a805000248db1fcdc51433c77fc887b648ee0d142e7e5db672cdc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1917465/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1917465/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,725,778,782,883,27911,27912,53778,53780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=6876192$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2164863$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carr, R.D.</creatorcontrib><creatorcontrib>Higgs, L.</creatorcontrib><creatorcontrib>Killingback, P.G.</creatorcontrib><creatorcontrib>Nicol, A.K.</creatorcontrib><creatorcontrib>O'Connor, S.E.</creatorcontrib><creatorcontrib>Robson, A.</creatorcontrib><creatorcontrib>Wells, E.</creatorcontrib><creatorcontrib>Simpson, W.T.</creatorcontrib><title>Pharmacological properties of FPL 63547, a novel inhibitor of angiotensin‐converting enzyme</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>1
FPL 63547, in its active diacid form, was a potent inhibitor of rabbit lung angiotensin converting enzyme (ACE) in vitro (IC50 0.51 nm).
2
In conscious normotensive dogs, FPL 63547 (10–300 μg kg−1 i.v.) produced prolonged, dose‐related inhibition of plasma ACE activity and angiotensin I pressor responses, without affecting basal blood pressure, heart rate or pressor responses to angiotensin II.
3
In anaesthetized dogs, FPL 63547 diacid (3–300 μg kg−1 i.v. cumulatively) produced dose‐related increases in cardiac output accompanied by falls in total peripheral resistance indicative of vasodilatation. Mild stimulation of cardiac rate and contractility was also observed. Enalapril diacid had a similar profile.
4
FPL 63547 was a highly effective antihypertensive agent after oral administration to spontaneously hypertensive rats (SHR) pretreated with a diuretic. It lowered systolic blood pressure (SBP) on acute administration over the range 3 × 10−7–10−5 mol kg−1 p.o. (⋍ 0.13–4.5 mg kg−1 p.o.). FPL 63547 was more potent than other ACE inhibitors tested, threshold active doses for lisinopril, enalapril and captopril being 10−6, 10−6 and 3 × 10−5 mol kg−1 p.o., respectively. The antihypertensive effects of FPL 63547, unlike those of enalapril and captopril, were of long duration.
5
The antihypertensive efficacy of FPL 63547 was also observed following chronic oral administration. A dose of 0.5 mg kg−1 day−1 once daily for 23 days produced a sustained reduction of SBP. By the end of the treatment period, SBP was significantly lowered both pre‐ and post‐dose, i.e. effective 24 h control had been achieved.
6
The profile of FPL 63547 is consistent with it being a potent, selective and long‐acting ACE inhibitor. As an antihypertensive agent in SHR it compared favourably with other members of this class with respect to potency and duration of action.</description><subject>Angiotensin I - pharmacology</subject><subject>Angiotensin-Converting Enzyme Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Antihypertensive agents</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Cardiac Output - drug effects</subject><subject>Cardiovascular system</subject><subject>Dogs</subject><subject>Dose-Response Relationship, Drug</subject><subject>Heart Rate - drug effects</subject><subject>Lung - drug effects</subject><subject>Lung - enzymology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Peptidyl-Dipeptidase A - blood</subject><subject>Pharmacology. Drug treatments</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Thiadiazoles - pharmacology</subject><subject>Vasodilation - drug effects</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkd1u0zAYhi3ENMrgEpAihDgiwXb8Fw4QbGIbUiV6AIfIchyndZXYnZ12K0dcAte4K5lDowqOED6xpff5Pr3WA8BLBAuUztt1gQhnOS0FKlBVwWKoEYaUFXePwOwYPQYzCCHPERLiCXga4xrCFHJ6Ck4xYkSwcga-L1Yq9Er7zi-tVl22CX5jwmBNzHybXS7mGSsp4W8ylTm_M11m3crWdvBhzJVbWj8YF627__lLe7cbZ90yM-7HvjfPwEmrumieT_cZ-Hb56evFdT7_cvX54uM816koy3Hdsjo11mWlBKSpNSaiqVGrG00RKUvNeauF4HVqbQxsEMGGG9rUjOPElGfg_WHvZlv3ptHGDUF1chNsr8JeemXl34mzK7n0O4kqxAmjacHraUHwN1sTB9nbqE3XKWf8NkpeCcEo5v8EEWWYEUgS-O4A6uBjDKY9tkFQjhblWo6q5KhKjhblZFHepeEXf_7nODppS_mrKVcxSWuDctrGI8YEZ6jCCftwwG5tZ_b_UUCeL65_P8sHsYu8Kg</recordid><startdate>199005</startdate><enddate>199005</enddate><creator>Carr, R.D.</creator><creator>Higgs, L.</creator><creator>Killingback, P.G.</creator><creator>Nicol, A.K.</creator><creator>O'Connor, S.E.</creator><creator>Robson, A.</creator><creator>Wells, E.</creator><creator>Simpson, W.T.</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M81</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>199005</creationdate><title>Pharmacological properties of FPL 63547, a novel inhibitor of angiotensin‐converting enzyme</title><author>Carr, R.D. ; Higgs, L. ; Killingback, P.G. ; Nicol, A.K. ; O'Connor, S.E. ; Robson, A. ; Wells, E. ; Simpson, W.T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5386-2bf6b381c39a805000248db1fcdc51433c77fc887b648ee0d142e7e5db672cdc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Angiotensin I - pharmacology</topic><topic>Angiotensin-Converting Enzyme Inhibitors - pharmacology</topic><topic>Animals</topic><topic>Antihypertensive agents</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Cardiac Output - drug effects</topic><topic>Cardiovascular system</topic><topic>Dogs</topic><topic>Dose-Response Relationship, Drug</topic><topic>Heart Rate - drug effects</topic><topic>Lung - drug effects</topic><topic>Lung - enzymology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Peptidyl-Dipeptidase A - blood</topic><topic>Pharmacology. Drug treatments</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Rats, Inbred SHR</topic><topic>Thiadiazoles - pharmacology</topic><topic>Vasodilation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carr, R.D.</creatorcontrib><creatorcontrib>Higgs, L.</creatorcontrib><creatorcontrib>Killingback, P.G.</creatorcontrib><creatorcontrib>Nicol, A.K.</creatorcontrib><creatorcontrib>O'Connor, S.E.</creatorcontrib><creatorcontrib>Robson, A.</creatorcontrib><creatorcontrib>Wells, E.</creatorcontrib><creatorcontrib>Simpson, W.T.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 3</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carr, R.D.</au><au>Higgs, L.</au><au>Killingback, P.G.</au><au>Nicol, A.K.</au><au>O'Connor, S.E.</au><au>Robson, A.</au><au>Wells, E.</au><au>Simpson, W.T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacological properties of FPL 63547, a novel inhibitor of angiotensin‐converting enzyme</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>1990-05</date><risdate>1990</risdate><volume>100</volume><issue>1</issue><spage>83</spage><epage>89</epage><pages>83-89</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>1
FPL 63547, in its active diacid form, was a potent inhibitor of rabbit lung angiotensin converting enzyme (ACE) in vitro (IC50 0.51 nm).
2
In conscious normotensive dogs, FPL 63547 (10–300 μg kg−1 i.v.) produced prolonged, dose‐related inhibition of plasma ACE activity and angiotensin I pressor responses, without affecting basal blood pressure, heart rate or pressor responses to angiotensin II.
3
In anaesthetized dogs, FPL 63547 diacid (3–300 μg kg−1 i.v. cumulatively) produced dose‐related increases in cardiac output accompanied by falls in total peripheral resistance indicative of vasodilatation. Mild stimulation of cardiac rate and contractility was also observed. Enalapril diacid had a similar profile.
4
FPL 63547 was a highly effective antihypertensive agent after oral administration to spontaneously hypertensive rats (SHR) pretreated with a diuretic. It lowered systolic blood pressure (SBP) on acute administration over the range 3 × 10−7–10−5 mol kg−1 p.o. (⋍ 0.13–4.5 mg kg−1 p.o.). FPL 63547 was more potent than other ACE inhibitors tested, threshold active doses for lisinopril, enalapril and captopril being 10−6, 10−6 and 3 × 10−5 mol kg−1 p.o., respectively. The antihypertensive effects of FPL 63547, unlike those of enalapril and captopril, were of long duration.
5
The antihypertensive efficacy of FPL 63547 was also observed following chronic oral administration. A dose of 0.5 mg kg−1 day−1 once daily for 23 days produced a sustained reduction of SBP. By the end of the treatment period, SBP was significantly lowered both pre‐ and post‐dose, i.e. effective 24 h control had been achieved.
6
The profile of FPL 63547 is consistent with it being a potent, selective and long‐acting ACE inhibitor. As an antihypertensive agent in SHR it compared favourably with other members of this class with respect to potency and duration of action.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>2164863</pmid><doi>10.1111/j.1476-5381.1990.tb12056.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Angiotensin I - pharmacology Angiotensin-Converting Enzyme Inhibitors - pharmacology Animals Antihypertensive agents Biological and medical sciences Blood Pressure - drug effects Cardiac Output - drug effects Cardiovascular system Dogs Dose-Response Relationship, Drug Heart Rate - drug effects Lung - drug effects Lung - enzymology Male Medical sciences Peptidyl-Dipeptidase A - blood Pharmacology. Drug treatments Rabbits Rats Rats, Inbred SHR Thiadiazoles - pharmacology Vasodilation - drug effects |
title | Pharmacological properties of FPL 63547, a novel inhibitor of angiotensin‐converting enzyme |
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