Donitriptan (; developmental code name F-11356) is a triptan drug which was investigated as an antimigraine agent but was never marketed. It acts as a selective serotonin 5-HT1B and 5-HT1D receptor agonist. The drug reached phase 2 clinical trials prior to the discontinuation of its development.
Pharmacology + Target Affinity (Ki, nM) 5-HT1A 12–25 (Ki)182–1,150 () 5-HT1B 0.08–0.36 (Ki)0.10–1.8 ()94–100% () 5-HT1D 0.06–0.48 (Ki)0.27–0.83 ()97–99% () 5-HT1E 1,150–1,700 (Ki)>10,000 () 5-HT1F 3,390–6,610 (Ki)>10,000 () 5-HT2A 182–447 (Ki)7.9 () 5-HT2B 813 (Ki)25 () 5-HT2C 575 (Ki) (rat) () 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 () α1A–α1D α2A–α2C β1–β3 D1 >10,000 D2 >10,000 D3–D5 H1 >10,000 H2 >10,000 H3, H4 M1–M5 mACh >10,000 I1, I2 >1,000 σ1, σ2 >1,000 () >1,000 () >1,000 () >10,000 >10,000 Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs:
Donitriptan acts as a high-affinity, high-efficacy near-full agonist of the serotonin 5-HT1B (Ki = 0.079–0.40nM; = 94%) and 5-HT1D receptors (Ki = 0.063–0.50nM; = 97%), and is among the most potent of the triptan series of drugs. It is also notable and unique among most of the triptans in being a potent serotonin 5-HT2A receptor agonist ( = 7.9nM), albeit with about one or two orders of magnitude lower activational potency than at the serotonin 5-HT1B and 5-HT1D receptors.
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.
The predicted log P of donitriptan is 1.32 to 2.2.
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.
See also Triptan Avitriptan
References