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Moexipril, a new angiotensin-converting enzyme (ACE) inhibitor: pharmacological characterization and comparison with enalapril

Moexipril, a new angiotensin-converting enzyme (ACE) inhibitor: pharmacological characterization and comparison with enalapril
Moexipril, a new angiotensin-converting enzyme (ACE) inhibitor: pharmacological characterization and comparison with enalapril
The pharmacodynamic profile of the new angiotensin-converting enzyme (ACE) inhibitor moexipril and its active diacid, moexiprilat, was studied in vitro and in vivo. In vitro, moexiprilat exhibited a higher inhibitory potency than enalaprilat against both plasma ACE and purified ACE from rabbit lung. Upon oral administration of moexipril (10 mg/kg/day) to spontaneously hypertensive rats, plasma angiotensin II concentration decreased to undetectable levels, plasma ACE activity was inhibited by 98% and plasma angiotensin I concentration increased 8.6-fold 1 h after dosing. At 24 h, plasma angiotensin I and angiotensin II concentrations had returned to pretreatment levels, whereas plasma ACE activity was still inhibited by 56%. Four-week oral administration of moexipril (0.1-30 mg/kg/day) to spontaneously hypertensive rats lowered blood pressure and differentially inhibited ACE activity in plasma, lung, aorta, heart and kidney in a dose-dependent fashion. Equidose treatment (10 mg/kg/day) with moexipril and enalapril over 4 weeks led to comparable decreases in blood pressure, inhibition of plasma ACE and reduction of plasma angiotensinogen and to a similar attenuation of the pressor responses to angiotensin I and potentiation of the depressor responses to bradykinin. In contrast, ACE inhibition in aorta, heart and lung was significantly greater with moexipril than with enalapril, whereas in the kidney both drugs inhibited ACE activity to a similar extent. In summary, moexipril is an orally active ACE inhibitor that is comparable to enalapril in potency and duration of antihypertensive activity. The results of the present study demonstrate that 1) the antihypertensive potency of a given ACE inhibitor cannot be predicted from its in vitro characteristics and 2) the degree of blood pressure reduction does not correlate with tissue ACE inhibition.
0022-3565
854-863
Edling, Oliver
609f04e6-fd95-44bc-a943-05019149d839
Bao, Gang
e0c20788-bf2b-4534-a9ce-bd66d9662cc2
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Unger, Thomas
337be77f-b72e-490e-b00c-47a9e0668edc
Gohlke, Peter
67e5e503-4d77-4789-a2cf-f6ac3a33bc3a
Edling, Oliver
609f04e6-fd95-44bc-a943-05019149d839
Bao, Gang
e0c20788-bf2b-4534-a9ce-bd66d9662cc2
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Unger, Thomas
337be77f-b72e-490e-b00c-47a9e0668edc
Gohlke, Peter
67e5e503-4d77-4789-a2cf-f6ac3a33bc3a

Edling, Oliver, Bao, Gang, Feelisch, Martin, Unger, Thomas and Gohlke, Peter (1995) Moexipril, a new angiotensin-converting enzyme (ACE) inhibitor: pharmacological characterization and comparison with enalapril. The Journal of Pharmacology and Experimental Therapeutics, 275 (2), 854-863. (PMID:7473177)

Record type: Article

Abstract

The pharmacodynamic profile of the new angiotensin-converting enzyme (ACE) inhibitor moexipril and its active diacid, moexiprilat, was studied in vitro and in vivo. In vitro, moexiprilat exhibited a higher inhibitory potency than enalaprilat against both plasma ACE and purified ACE from rabbit lung. Upon oral administration of moexipril (10 mg/kg/day) to spontaneously hypertensive rats, plasma angiotensin II concentration decreased to undetectable levels, plasma ACE activity was inhibited by 98% and plasma angiotensin I concentration increased 8.6-fold 1 h after dosing. At 24 h, plasma angiotensin I and angiotensin II concentrations had returned to pretreatment levels, whereas plasma ACE activity was still inhibited by 56%. Four-week oral administration of moexipril (0.1-30 mg/kg/day) to spontaneously hypertensive rats lowered blood pressure and differentially inhibited ACE activity in plasma, lung, aorta, heart and kidney in a dose-dependent fashion. Equidose treatment (10 mg/kg/day) with moexipril and enalapril over 4 weeks led to comparable decreases in blood pressure, inhibition of plasma ACE and reduction of plasma angiotensinogen and to a similar attenuation of the pressor responses to angiotensin I and potentiation of the depressor responses to bradykinin. In contrast, ACE inhibition in aorta, heart and lung was significantly greater with moexipril than with enalapril, whereas in the kidney both drugs inhibited ACE activity to a similar extent. In summary, moexipril is an orally active ACE inhibitor that is comparable to enalapril in potency and duration of antihypertensive activity. The results of the present study demonstrate that 1) the antihypertensive potency of a given ACE inhibitor cannot be predicted from its in vitro characteristics and 2) the degree of blood pressure reduction does not correlate with tissue ACE inhibition.

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Published date: November 1995
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337897
URI: https://eprints.soton.ac.uk/id/eprint/337897
ISSN: 0022-3565
PURE UUID: 99703497-e28e-4310-b13b-ba8c01d55957
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 29 Jun 2012 15:32
Last modified: 06 Jun 2018 12:29

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