Avitriptan (INNTooltip International Nonproprietary Name; development code BMS-180048) is an antimigraine drug of the triptan family which was never marketed. It acts as a serotonin 5-HT1B and 5-HT1D receptor agonist. The drug reached phase 3 clinical trials prior to the discontinuation of its development.

Pharmacology

Avitriptan activities
TargetAffinity (Ki, nM)
5-HT1A19 (Ki) 646–>10,000 (EC50Tooltip half-maximal effective concentration)
5-HT1B1.6–21 (Ki) 2.1–2.7 (EC50)
5-HT1D0.78–4.4 (Ki) 0.54 (EC50)
5-HT1E3,550 (Ki) 3,020–>10,000 (EC50)
5-HT1F78–182 (Ki) 81–891 (EC50)
5-HT2A2,340 (Ki) 123 (EC50)
5-HT2B1,150 (Ki) 389 (EC50)
5-HT2CND (Ki) ND (EC50)
5-HT3>1,000 (rat)
5-HT4ND
5-HT5AND
5-HT6ND
5-HT7759 (Ki) 4,170 (EC50)
α1Aα1DND
α2Aα2CND
β1β3ND
D1D5ND
H1H4ND
M1M5ND
I1, I2ND
σ1, σ2ND
TAAR1Tooltip Trace amine-associated receptor 1ND
SERTTooltip Serotonin transporterND
NETTooltip Norepinephrine transporterND
DATTooltip Dopamine transporterND
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs:

Avitriptan acts as a selective serotonin 5-HT1B and 5-HT1D receptor agonist. It is also notable in being a weak serotonin 5-HT2A receptor agonist (EC50Tooltip half-maximal effective concentration = 123nM), albeit with about two orders of magnitude lower activational potency than at the serotonin 5-HT1B and 5-HT1D receptors.

Besides its activities at serotonin receptors, avitriptan has been found to act as a weak aryl hydrocarbon receptor agonist.

Chemistry

Avitriptan is a triptan and a modified analogue of tryptamines like the psychedelic drug dimethyltryptamine (DMT). However, avitriptan itself is not technically a tryptamine as it features a propylamine side chain instead of the ethylamine side chain present in tryptamines. Besides this difference, avitriptan is substituted at the 5 position of the indole ring system and the amine moiety has been cyclized and extended.

The predicted log P of avitriptan is 1.8.

See also