A clinical and biochemical assessment of a nonthiol ACE inhibitor (pentopril; CGS-13945) in active rheumatoid arthritis.
Captopril, which is a thiol containing angiotensin converting enzyme (ACE) inhibitor that has a close structural similarity to D-penicillamine, behaves as a disease modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA). In order to ascertain whether the DMARD-like properties of captopril reside in its ability to inhibit ACE or in the thiol group, we evaluated pentopril (CGS-13945) in patients with active RA. This recently synthesized drug is a nonthiol containing ACE inhibitor. Pentopril produced little clinical improvement and no biochemical improvement in a group of 15 patients with RA, many of whom were unable to tolerate it because of in-effect or side effects. A reduction in serum ACE activity and a modest fall in blood pressure suggested that the drug was exerting its pharmacological effect. Our study strengthens the argument that the therapeutic benefit of captopril in RA probably lies in its thiol group rather than in its enzyme inhibition properties, and that the thiol group may be the effective moiety in some other DMARD.
Bird
H A
HA
Clinical Pharmacology Unit, Royal Bath Hospital, Harrogate, North Yorkshire, UK.
Le Gallez
P
P
Dixon
J S
JS
Catalano
M A
MA
Traficante
A
A
Liauw
L A
LA
Sussman
H
H
Rotman
H
H
Wright
V
V
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007596:Joints / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010146:Pain
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C038810:CGS 13945