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Donitriptan

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Donitriptan
Clinical data
Drug classSerotonin 5-HT1B and 5-HT1D receptor agonist; Antimigraine agent
ATC code
  • None
Legal status
Legal status
  • Never marketed
Identifiers
  • 4-[4-({[3-(2-Aminoethyl)-1H-indol-5-yl]oxy}acetyl)-1-piperazinyl]benzonitrile
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H25N5O2
Molar mass403.486 g·mol−1
3D model (JSmol)
  • c1cc(ccc1C#N)N2CCN(CC2)C(=O)COc3ccc4c(c3)c(c[nH]4)CCN
  • InChI=1S/C23H25N5O2/c24-8-7-18-15-26-22-6-5-20(13-21(18)22)30-16-23(29)28-11-9-27(10-12-28)19-3-1-17(14-25)2-4-19/h1-6,13,15,26H,7-12,16,24H2
  • Key:SOHCKWZVTCTQBG-UHFFFAOYSA-N

Donitriptan (INN; code name F-11356) is a triptan drug which was investigated as an antimigraine agent but ultimately was never marketed.[1][2]

Pharmacology

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The drug acts as a high-affinity, high-efficacy near-full agonist of the serotonin 5-HT1B (pKi = 9.4–10.1; IA = 94%) and 5-HT1D receptors (pKi = 9.3–10.2; IA = 97%), and is among the most potent of the triptan series of drugs.[2][3][4][5] It is also notable and unique among most of the triptans in being a potent serotonin 5-HT2A receptor agonist (EC50Tooltip half-maximal effective concentration = 7.94 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

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The predicted log P of donitriptan is 1.32 to 2.2.[7][8]

History

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Donitriptan was being developed in France by bioMérieux-Pierre Fabre and made it to phase II clinical trials in Europe before development was discontinued.[9][10][11][2]

References

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  1. ^ Dukat M (March 2001). "Donitriptan (Pierre Fabre)". Current Opinion in Investigational Drugs. 2 (3): 415–418. PMID 11575714.
  2. ^ a b c Perez, M.; Halazy, S.; Pauwels, P.J.; Colpaert, F.C.; John, G.W. (1999). "F-11356". Drugs of the Future. 24 (6): 0605. doi:10.1358/dof.1999.024.06.537284. Retrieved 23 June 2025.
  3. ^ Perez M, Fourrier C, Sigogneau I, Pauwels PJ, Palmier C, John GW, et al. (September 1995). "Synthesis and serotonergic activity of arylpiperazide derivatives of serotonin: potent agonists for 5-HT1D receptors". Journal of Medicinal Chemistry. 38 (18): 3602–3607. doi:10.1021/jm00018a020. PMID 7658447.
  4. ^ Saxena PR, Tfelt-Hansen P (2006). "Triptans, 5-HT1B/1D Receptor Agonists in the Acute Treatment of Migraine". In Olesen J (ed.). The Headaches. Lippincott Williams & Wilkins. pp. 470–. ISBN 978-0-7817-5400-2.
  5. ^ John GW, Pauwels PJ, Perez M, Halazy S, Le Grand B, Verscheure Y, et al. (July 1999). "F 11356, a novel 5-hydroxytryptamine (5-HT) derivative with potent, selective, and unique high intrinsic activity at 5-HT1B/1D receptors in models relevant to migraine". The Journal of Pharmacology and Experimental Therapeutics. 290 (1): 83–95. doi:10.1016/S0022-3565(24)34871-2. PMID 10381763.
  6. ^ Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, van den Bogaerdt A, Bogers AJ, Zanelli E, Meeus L, Danser AH, Gralinski MR, Senese PB, Johnson KW, Kovalchin J, Villalón CM, MaassenVanDenBrink A (December 2019). "Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan". British Journal of Pharmacology. 176 (24): 4681–4695. doi:10.1111/bph.14832. PMC 6965684. PMID 31418454. TABLE 1 Summary of pIC50 (negative logarithm of the molar concentration of these compounds at which 50% of the radioligand is displaced) and pKi (negative logarithm of the molar concentration of the Ki ) values of individual antimigraine drugs at 5‐HT receptors [...] TABLE 2 Summary of pEC50 values of cAMP (5‐HT1A/B/E/F and 5‐HT7), GTPγS (5‐HT1A/B/D/E/F), and IP (5‐HT2) assays of individual antimigraine drugs at 5‐HT receptors [...]
  7. ^ "Donitriptan". PubChem. Retrieved 24 June 2025.
  8. ^ "donitriptan". ChemSpider. 10 June 2024. Retrieved 24 June 2025.
  9. ^ Schmidt WK (28 May 2013). "An Overview of Current and Investigational Drugs for the Treatment of Acute and Chronic Pain". In Bountra C, Munglani R, Schmidt WK (eds.). Pain: Current Understanding, Emerging Therapies, and Novel Approaches to Drug Discovery. CRC Press. pp. 402–. ISBN 978-0-203-91125-9.
  10. ^ Fleischhacker WW, Brooks DJ (21 May 2003). Neuropsychopharmacology. Springer Vienna. pp. 38–. ISBN 978-3-211-83903-4.
  11. ^ Tepper SJ (2004). "New Areas of Research". Understanding Migraine and Other Headaches. Univ. Press of Mississippi. pp. 118. ISBN 978-1-60473-048-7.
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