Inhibitors of enkephalin-degrading enzymes as potential therapeutic agents.
A limited number of enzymes such as membrane metalloendopeptidase (enkephalinase) and angiotensin converting enzyme appear to be involved in deactivation and modulation of circulatory regulatory peptides. Peptides such as the enkephalins are also involved in a large number of physiological processes. This multiplicity of physiological roles has made it difficult to establish the therapeutic role of enkephalin-degrading enzyme inhibitors. Other factors such as difficulty in quantification and thus measurement of processes involved in pain and mental illness have also hindered the process of establishing any therapeutic role of enkephalin-degrading enzyme inhibitors in these conditions. However, they have proved to be useful pharmacological 'tools'. The most likely therapeutic role at present appears to be in the treatment of cardiovascular disorders. As a 'profile' of pharmacological actions of enkephalin-degrading enzymes emerges, it is becoming apparent that bioavailability rather than a high degree of specificity or inhibitory potency may be the most important factor. This may be used to an advantage in future developments by the use of less specific or combined inhibitors in the form of prodrugs, designed to be active at specific sites such as the central nervous system.
Patel
A
A
Welsh School of Pharmacy, University of Wales, Cardiff, U.K.
Smith
H J
HJ
Sewell
R D
RD
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D002317:Cardiovascular Agents; D004745:Enkephalins / Q000378:metabolism*; D006801:Humans
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D002317:Cardiovascular Agents; D004745:Enkephalins; D000626:Aminopeptidases; C025579:enkephalin degrading enzyme