Donitriptan
Chemical compound
From Wikipedia, the free encyclopedia
Donitriptan (INN; developmental code name F-11356) is a triptan drug which was investigated as an antimigraine agent but was never marketed.[1][2][3] It acts as a selective serotonin 5-HT1B and 5-HT1D receptor agonist.[4][5][6][3] The drug reached phase 2 clinical trials prior to the discontinuation of its development.[7]
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| Other names | F-11356; F11356; F-12640; F12640 |
| Drug class | Serotonin 5-HT1B and 5-HT1D receptor agonist; Antimigraine agent; Triptan |
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| Formula | C23H25N5O2 |
| Molar mass | 403.486 g·mol−1 |
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Pharmacology
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 12–25 (Ki) 182–1,150 (EC50) |
| 5-HT1B | 0.08–0.36 (Ki) 0.10–1.8 (EC50) 94–100% (Emax) |
| 5-HT1D | 0.06–0.48 (Ki) 0.27–0.83 (EC50) 97–99% (Emax) |
| 5-HT1E | 1,150–1,700 (Ki) >10,000 (EC50) |
| 5-HT1F | 3,390–6,610 (Ki) >10,000 (EC50) |
| 5-HT2A | 182–447 (Ki) 7.9 (EC50) |
| 5-HT2B | 813 (Ki) 25 (EC50) |
| 5-HT2C | 575 (Ki) (rat) ND (EC50) |
| 5-HT3 | >10,000 (mouse) |
| 5-HT4 | 2,000 (guinea pig) |
| 5-HT5A | 813 |
| 5-HT6 | 2,340 |
| 5-HT7 | 372–617 (Ki) 5,890 (EC50) |
| α1A–α1D | ND |
| α2A–α2C | ND |
| β1–β3 | ND |
| D1 | >10,000 |
| D2 | >10,000 |
| D3–D5 | ND |
| H1 | >10,000 |
| H2 | >10,000 |
| H3, H4 | ND |
| M1–M5 | ND |
| mACh | >10,000 |
| I1, I2 | >1,000 |
| σ1, σ2 | ND |
| TAAR1 | ND |
| SERT | >1,000 (IC50) |
| NET | >1,000 (IC50) |
| DAT | >1,000 (IC50) |
| MAO-A | >10,000 |
| MAO-B | >10,000 |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [4][5][8][9][6][3] | |
Donitriptan acts as a high-affinity, high-efficacy near-full agonist of the serotonin 5-HT1B (Ki = 0.079–0.40 nM; Emax = 94%) and 5-HT1D receptors (Ki = 0.063–0.50 nM; Emax = 97%), and is among the most potent of the triptan series of drugs.[3][10][11][4] It is also notable and unique among most of the triptans in being a potent serotonin 5-HT2A receptor agonist (EC50 = 7.9 nM), albeit with about one or two orders of magnitude lower activational potency than at the serotonin 5-HT1B and 5-HT1D receptors.[6]
Chemistry
Donitriptan is a tryptamine derivative, a 5-substituted derivative of tryptamine and 5-methoxytryptamine, and an analogue of the psychedelic drugs dimethyltryptamine (DMT) and 5-MeO-DMT.[12]
History
Donitriptan was being developed in France by bioMérieux-Pierre Fabre and made it to phase II clinical trials in Europe before development was discontinued.[14][15][16][3]