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Remarkably, its putative mechanism of action has only been recently elucidated, particularly because of the cloning of a G protein\u2010coupled receptor (HM74A or GPR109A). This receptor responds to both nicotinic acid and the ketone body \u03b2\u2010hydroxybutyrate, the latter thought to be the more probable endogenous ligand for HM74A. In this review, we will discuss the pharmacology and medicinal chemistry of this receptor subtype and a related one (HM74 or GPR109B). Although still in its infancy, the ligand repertoire is developing, and a number of compound classes have now been described, among which are both full and partial agonists. Antagonists, however, are still lacking, thus compromising thorough pharmacological studies. Mutagenesis experiments have provided clues regarding the ligand binding site; in particular, an arginine residue in transmembrane domain 3 of the receptor seems to recognize the acidic moiety present in nicotinic acid and related substances. HM74A has also been linked to one of the major side effects of nicotinic acid, that is, flushing, since this receptor subtype also occurs in skin immune cells. It is not known yet whether HM74 is also present on these cells. Since nicotinic acid is one of the few available medicines that raise HDL (\u201cgood cholesterol\u201d) levels, HM74A and HM74 appear promising targets for future pharmacotherapy. \u00a9 2007 Wiley Periodicals, Inc. Med Res Rev, 27, No. 3, 417\u2013433, 2007<\/jats:p>","DOI":"10.1002\/med.20102","type":"journal-article","created":{"date-parts":[[2007,1,19]],"date-time":"2007-01-19T22:13:59Z","timestamp":1169244839000},"page":"417-433","source":"Crossref","is-referenced-by-count":77,"title":["Nicotinic acid receptor subtypes and their ligands"],"prefix":"10.1002","volume":"27","author":[{"given":"Willem","family":"Soudijn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ineke","family":"van Wijngaarden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan P.","family":"IJzerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,1,19]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(55)90070-9"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(64)90149-3"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)93503-9"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(80)80715-0"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(83)80254-3"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.59.2.349"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01220-0"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200112)31:12<3714::AID-IMMU3714>3.0.CO;2-1"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/5.10.1239"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.7.1723"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210695200"},{"key":"e_1_2_1_13_2","unstructured":"Bristol\u2010Myers Squibb Company. 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