Avitriptan

Avitriptan
Clinical data
Other names	BMS-180048; BMS-180,048; BMS180048
Drug class	Serotonin 5-HT1B and 5-HT1D receptor agonist; Antimigraine agent; Triptan
ATC code	None;
Legal status
Legal status	Never marketed;
Identifiers
	IUPAC name 1-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1H-indol-5-yl]-N-methyl-methanesulfonamide;
CAS Number	151140-96-4 Y;
PubChem CID	133081;
ChemSpider	117442 Y;
UNII	6RS056L04P;
KEGG	D03014 Y;
ChEMBL	ChEMBL2105880 Y;
CompTox Dashboard (EPA)	DTXSID60164718 ;
Chemical and physical data
Formula	C22H30N6O3S
Molar mass	458.58 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=S(=O)(NC)Cc1ccc2c(c1)c(c[nH]2)CCCN4CCN(c3ncncc3OC)CC4;
	InChI 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 Y; Key:WRZVGHXUPBWIOO-UHFFFAOYSA-N Y;
	(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-HT_1B and 5-HT_1D receptor agonist.¹² The drug reached phase 3 clinical trials prior to the discontinuation of its development.³

Pharmacology

Avitriptan activities
Target	Affinity (K_i, nM)
5-HT_1A	19 (K_i) 646–>10,000 (EC₅₀Tooltip half-maximal effective concentration)
5-HT_1B	1.6–21 (K_i) 2.1–2.7 (EC₅₀)
5-HT_1D	0.78–4.4 (K_i) 0.54 (EC₅₀)
5-HT_1E	3,550 (K_i) 3,020–>10,000 (EC₅₀)
5-HT_1F	78–182 (K_i) 81–891 (EC₅₀)
5-HT_2A	2,340 (K_i) 123 (EC₅₀)
5-HT_2B	1,150 (K_i) 389 (EC₅₀)
5-HT_2C	ND (K_i) ND (EC₅₀)
5-HT₃	>1,000 (rat)
5-HT₄	ND
5-HT_5A	ND
5-HT₆	ND
5-HT₇	759 (K_i) 4,170 (EC₅₀)
α_1A–α_1D	ND
α_2A–α_2C	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: ¹⁴²

Avitriptan acts as a selective serotonin 5-HT_1B and 5-HT_1D receptor agonist.¹² It is also notable in being a weak serotonin 5-HT_2A receptor agonist (EC₅₀Tooltip half-maximal effective concentration = 123 nM), albeit with about two orders of magnitude lower activational potency than at the serotonin 5-HT_1B and 5-HT_1D 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 propyl amine side chain instead of the ethyl amine 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

References

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.
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-HT_1F 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 [...]
"Delving into the Latest Updates on Avitriptan with Synapse". Synapse. 19 July 2025. Retrieved 29 July 2025.
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.
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.
"Avitriptan". PubChem. Retrieved 29 July 2025.

[SaxenaDeVriesWang1997-1] 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.

[Rubio-BeltránLabastida-RamírezHaanes2019-2] 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-HT_1F 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 [...]

[AdisInsight-3] "Delving into the Latest Updates on Avitriptan with Synapse". Synapse. 19 July 2025. Retrieved 29 July 2025.

[RamadanSkljarevskiPhebus2003-4] 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.

[VyhlídalováKrasulováPečinková2020-5] 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.

[PubChem-6] "Avitriptan". PubChem. Retrieved 29 July 2025.

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Pharmacology

Chemistry

See also

References