Avitriptan

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.^[1][2] The drug reached phase 3 clinical trials prior to the discontinuation of its development.^[3]

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
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Pharmacology

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-HT_1B and 5-HT_1D receptor agonist.^[1][2] 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 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

• Triptan
• Donitriptan