[New antilipemics: prospects].
The field of new lipid-lowering drug research is very active, with researchers, looking to make the currently available drugs more powerful and safer, and to develop new classes of drugs. Among the statins, development has gone the farthest for rosuvastatin and pitavastatin. Colesevelam is a new bile acid sequestrant with a better digestive tolerance. Among the new classes of drugs, the most promising molecules are the cholesterol absorption inhibitors--with ezetimibe as the first in line--and the PPAR-alpha and PPAR-gamma activators. Among the other classes, the acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors, microsomal triglyceride transfer protein (MTP) inhibitors, cholesteryl ester transfer protein (CETP) inhibitors, and ileal bile acid transporter inhibitors, have to be mentioned. In most of the cases, those new compounds are being developed mainly as a combined treatment with statins. However, these combination therapies differ depending on the lipid abnormalities of the patient. The statin-ezitimibe and the statin-bile acid sequestrant combinations have been the most studied treatments in pure hypercholesterolaemia. On another hand, the statin-PPAR-alpha and -gamma activator combination were the first to be developed for patients with combined hyperlipidaemia or type 2 diabetes mellitus. However, the clinical benefit of ACAT or CETP inhibitors remains to be determined and the development of MTP inhibitors has been restricted so far, because of problems of digestive intolerance and hepatic steatosis. Finally, the discovery of new specific lipoprotein receptors, such as the ABCA1 and SRB1 receptors, means that we can work towards developing new potential targets for pharmacological intervention.
Farnier
Michel
M
mfarnier@ipac.fr
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D053480:Cholesterol Ester Transfer Proteins; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006023:Glycoproteins; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy*; D006949:Hyperlipidemias / Q000188:drug therapy*; D006951:Hyperlipoproteinemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007408:Intestinal Absorption / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000378:metabolism
D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C106092:microsomal triglyceride transfer protein; D002785:Sterol O-Acyltransferase