Avitriptan
Chemical compound
From Wikipedia, the free encyclopedia
Avitriptan (INN; development code BMS-180048) is an antimigraine drug of the triptan family which was never marketed.[1] It acts as a serotonin 5-HT1B and 5-HT1D receptor agonist.[1][2] The drug reached phase 3 clinical trials prior to the discontinuation of its development.[3]
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| Other names | BMS-180048; BMS-180,048; BMS180048 |
| Drug class | Serotonin 5-HT1B and 5-HT1D receptor agonist; Antimigraine agent; Triptan |
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| Formula | C22H30N6O3S |
| Molar mass | 458.58 g·mol−1 |
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Pharmacology
| Target | Affinity (Ki, nM) |
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| 5-HT1A | 19 (Ki) 646–>10,000 (EC50) |
| 5-HT1B | 1.6–21 (Ki) 2.1–2.7 (EC50) |
| 5-HT1D | 0.78–4.4 (Ki) 0.54 (EC50) |
| 5-HT1E | 3,550 (Ki) 3,020–>10,000 (EC50) |
| 5-HT1F | 78–182 (Ki) 81–891 (EC50) |
| 5-HT2A | 2,340 (Ki) 123 (EC50) |
| 5-HT2B | 1,150 (Ki) 389 (EC50) |
| 5-HT2C | ND (Ki) ND (EC50) |
| 5-HT3 | >1,000 (rat) |
| 5-HT4 | ND |
| 5-HT5A | ND |
| 5-HT6 | ND |
| 5-HT7 | 759 (Ki) 4,170 (EC50) |
| α1A–α1D | ND |
| α2A–α2C | ND |
| β1–β3 | ND |
| D1–D5 | ND |
| H1–H4 | ND |
| M1–M5 | ND |
| I1, I2 | ND |
| σ1, σ2 | ND |
| TAAR1 | ND |
| SERT | ND |
| NET | ND |
| DAT | ND |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [1][4][2] | |
Avitriptan acts as a selective serotonin 5-HT1B and 5-HT1D receptor agonist.[1][2] It is also notable in being a weak serotonin 5-HT2A receptor agonist (EC50 = 123 nM), albeit with about two orders of magnitude lower activational potency than at the serotonin 5-HT1B and 5-HT1D receptors.[2]
Besides its activities at serotonin receptors, avitriptan has been found to act as a weak aryl hydrocarbon receptor agonist.[5]
Chemistry
Avitriptan is a triptan and a modified analogue of tryptamines like the psychedelic drug dimethyltryptamine (DMT).[6] However, avitriptan itself is not technically a tryptamine as it features a propylamine side chain instead of the ethylamine side chain present in tryptamines.[6] Besides this difference, avitriptan is substituted at the 5 position of the indole ring system and the amine moiety has been cyclized and extended.[6]