Chemistry:Avitriptan

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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]

Pharmacology

Avitriptan activities
Target Affinity (Ki, nM)
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]

The predicted log P of avitriptan is 1.8.[6]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 "Effects of avitriptan, a new 5-HT 1B/1D receptor agonist, in experimental models predictive of antimigraine activity and coronary side-effect potential". Naunyn-Schmiedeberg's Archives of Pharmacology 355 (2): 295–302. February 1997. doi:10.1007/pl00004946. PMID 9050026. Archived from the original on 1999-10-23. https://web.archive.org/web/19991023052058/http://link.springer.de/link/service/journals/00210/bibs/7355002/73550295.htm. 
  2. ↑ 2.0 2.1 2.2 2.3 "Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan". British Journal of Pharmacology 176 (24): 4681–4695. December 2019. doi:10.1111/bph.14832. 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 [...]". 
  3. ↑ "Delving into the Latest Updates on Avitriptan with Synapse". 19 July 2025. https://synapse.patsnap.com/drug/78b57fbb4361494884d802e14e8ffd90. 
  4. ↑ "5-HT1F receptor agonists in acute migraine treatment: a hypothesis". Cephalalgia 23 (8): 776–785. October 2003. doi:10.1046/j.1468-2982.2003.00525.x. PMID 14510923. 
  5. ↑ "Antimigraine Drug Avitriptan Is a Ligand and Agonist of Human Aryl Hydrocarbon Receptor That Induces CYP1A1 in Hepatic and Intestinal Cells". Int J Mol Sci 21 (8): 2799. April 2020. doi:10.3390/ijms21082799. PMID 32316498. 
  6. ↑ 6.0 6.1 6.2 6.3 "Avitriptan". https://pubchem.ncbi.nlm.nih.gov/compound/133081. 



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