Jump to content

Avitriptan

From Wikipedia, the free encyclopedia
Avitriptan
Clinical data
Other namesBMS-180048; BMS-180,048; BMS180048
Drug classSerotonin 5-HT1B and 5-HT1D receptor agonist; Antimigraine agent; Triptan
ATC code
  • None
Legal status
Legal status
  • Never marketed
Identifiers
  • 1-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1H-indol-5-yl]-N-methyl-methanesulfonamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC22H30N6O3S
Molar mass458.58 g·mol−1
3D model (JSmol)
  • O=S(=O)(NC)Cc1ccc2c(c1)c(c[nH]2)CCCN4CCN(c3ncncc3OC)CC4
  • InChI=1S/C22H30N6O3S/c1-23-32(29,30)15-17-5-6-20-19(12-17)18(13-25-20)4-3-7-27-8-10-28(11-9-27)22-21(31-2)14-24-16-26-22/h5-6,12-14,16,23,25H,3-4,7-11,15H2,1-2H3 checkY
  • Key:WRZVGHXUPBWIOO-UHFFFAOYSA-N checkY
  (verify)

Avitriptan (INNTooltip International Nonproprietary Name; 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

[edit]
Avitriptan activities
Target Affinity (Ki, nM)
5-HT1A 19 (Ki)
646–>10,000 (EC50Tooltip half-maximal effective concentration)
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
TAAR1Tooltip Trace amine-associated receptor 1 ND
SERTTooltip Serotonin transporter ND
NETTooltip Norepinephrine transporter ND
DATTooltip Dopamine transporter 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 (EC50Tooltip half-maximal effective concentration = 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

[edit]

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

[edit]

References

[edit]
  1. ^ a b c d Saxena PR, De Vries P, Wang W, et al. (February 1997). "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. doi:10.1007/pl00004946. hdl:1765/66501. PMID 9050026. S2CID 25137165. Archived from the original on 1999-10-23.
  2. ^ a b c d 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 [...]
  3. ^ "Delving into the Latest Updates on Avitriptan with Synapse". Synapse. 19 July 2025. Retrieved 29 July 2025.
  4. ^ Ramadan NM, Skljarevski V, Phebus LA, Johnson KW (October 2003). "5-HT1F receptor agonists in acute migraine treatment: a hypothesis". Cephalalgia. 23 (8): 776–785. doi:10.1046/j.1468-2982.2003.00525.x. PMID 14510923.
  5. ^ Vyhlídalová B, Krasulová K, Pečinková P, Poulíková K, Vrzal R, Andrysík Z, Chandran A, Mani S, Dvorak Z (April 2020). "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. doi:10.3390/ijms21082799. PMC 7216230. PMID 32316498.
  6. ^ a b c d "Avitriptan". PubChem. Retrieved 29 July 2025.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Avitriptan&oldid=1303100096"