Asubstituted 3-benzazepine, or simply3-benzazepine, is aderivative of3-benzazepine.[2][3][4] They arecyclized phenethylamines and are closely related to thetetrahydroisoquinolines.[2][3] In addition, they are analogous to thecyclized tryptamineibogalogs and theirβ-carboline relatives.[5][6]
3-Benzazepines are known to act asmonoamine receptor modulators, including asdopamineD1-like receptoragonists, dopamineD1 receptorantagonists, andserotonin5-HT2A,5-HT2B, and5-HT2C receptor agonists, among other activities.[2][3][4][7][8][9][10] 3-Benzazepines acting as serotonin 5-HT2 receptor agonists generally show varying degrees of preferential activity at the serotonin 5-HT2C receptor over the serotonin 5-HT2A receptor, with occasional exceptions.[9] One 3-benzazepine, thenon-selective serotonin5-HT2 receptor agonist and previously marketedanorecticlorcaserin (Belviq), is known to producepsychedelic effects at supratherapeutic doses.[11]
| Structure | Name | Action | Chemical name | Ref |
|---|---|---|---|---|
 | 3-Benzazepine | N/A | 3H-3-benzazepine | |
 | SKF-39315 | D1-like agonist | 2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol | |
 | Lorcaserin | 5-HT2 agonist | (1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine | |
 | 7-Chlorolorcaserin | 5-HT2 agonist | (1R)-7,8-dichloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine | |
 | SCHEMBL5334361 | 5-HT2 agonist | 7-[(3-methoxyphenoxy)methyl]-2,3,4,5-tetrahydro-1H-3-benzazepine | |
 | SKF-38393 | D1-like agonist | 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol | |
| SKF-81297 | D1-like agonist | (1R)-6-chloro-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol | |
 | Fenoldopam | D1-like agonist | 6-chloro-1-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol | |
 | SCH-23390 | D1 antagonist | (5R)-8-chloro-3-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-ol | |
 | SKF-83959 | D1-like agonist | 6-chloro-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol | |
 | Trepipam (SCH-12679) | D1-like agonist | 7,8-dimethoxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine | |
 | SKF-77434 | D1-like agonist | (1R)-1-phenyl-3-(prop-2-en-1-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol | |
 | SKF-82958 | D1-like agonist | (1R)-6-chloro-1-phenyl-3-(prop-2-en-1-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol | |
 | 6-Br-APB | D1-like agonist | (1R)-6-bromo-1-phenyl-3-(prop-2-en-1-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol | |
 | Odapipam (NNC 01-0756) | D1 antagonist | (5S)-8-chloro-5-(2,3-dihydro-1-benzofuran-7-yl)-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol | |
 | Berupipam (NNC 22-0010) | D1 antagonist | (5S)-5-(5-bromo-2,3-dihydro-1-benzofuran-7-yl)-8-chloro-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol | |
 | NNC 01-0687 (ADX-10061, CEE-03-310) | D1 antagonist | (5S)-5-(2,3-dihydro-1-benzofuran-7-yl)-3-methyl-8-nitro-1,2,4,5-tetrahydro-3-benzazepin-7-ol | |
 | GSK-189254 | H3 antagonist | 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methylpyridine-3-carboxamide | |
 | Anilopam (PR 786-723) | Opioid | 4-[2-(7-methoxy-4-methyl-1,2,4,5-tetrahydro-3-benzazepin-3-yl)ethyl]aniline |
| Structure | Name | Action | Chemical name | Ref |
|---|---|---|---|---|
 | PF-04479745 | 5-HT2 modulator | (9S)-2-benzyl-N,9-dimethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine | |
 | PF-04781340 | 5-HT2 modulator | 3-benzyl-N-methyl-6,7,8,9-tetrahydro-5H-pyrido[3,4-d]azepin-1-amine |
[...] several lines of evidence suggest that lorcaserin also has actions at 5-HT2A receptors. First, in vitro functional studies suggest that lorcaserin is only modestly (~19-fold) selective for 5-HT2C over 5-HT2A receptors in vitro (Thomsen et al., 2008; also see Table 1), raising the possibility that the doses required to decrease intravenous drug self-administration are large enough to bind to and possibly exert effects at 5-HT2A receptors. Indeed, when evaluated in a sample of recreational polydrug users, doses only slightly larger (20-60 mg) than the maximally approved dose of 10 mg (administered twice daily [BID]) produced feelings of "high" and "bad effects", as well as perceptual changes that were described by a subset of subjects as "hallucination" and/or feeling "detached" and "spaced out" (Shram et al., 2011). Dose-dependent increases in other adverse effects (e.g., nausea, headache, dizziness, euphoric mood, etc.) were also noted, with most subjects (70-100%) reporting at least one adverse effect after receiving larger doses of lorcaserin (Shram et al., 2011).