Donitriptan

Donitriptan (INN; code name F-11356) is a triptan drug which was investigated as an antimigraine agent but ultimately was never marketed.^[1][2]

Donitriptan

Clinical data
Drug class	Serotonin 5-HT1B and 5-HT1D receptor agonist; Antimigraine agent
ATC code	None
Legal status
Legal status	Never marketed
Identifiers
IUPAC name 4-[4-({[3-(2-Aminoethyl)-1H-indol-5-yl]oxy}acetyl)-1-piperazinyl]benzonitrile
CAS Number	170912-52-4
PubChem CID	197706
ChemSpider	171128
UNII	70968BVH2J
ChEMBL	ChEMBL1742428
CompTox Dashboard (EPA)	DTXSID20168974
Chemical and physical data
Formula	C23H25N5O2
Molar mass	403.486 g·mol−1
3D model (JSmol)	Interactive image
SMILES c1cc(ccc1C#N)N2CCN(CC2)C(=O)COc3ccc4c(c3)c(c[nH]4)CCN
InChI InChI=1S/C23H25N5O2/c24-8-7-18-15-26-22-6-5-20(13-21(18)22)30-16-23(29)28-11-9-27(10-12-28)19-3-1-17(14-25)2-4-19/h1-6,13,15,26H,7-12,16,24H2 Key:SOHCKWZVTCTQBG-UHFFFAOYSA-N

Pharmacology

The drug acts as a high-affinity, high-efficacy near-full agonist of the serotonin 5-HT_1B (K_i = 0.079–0.40 nM; E_maxTooltip maximal efficacy = 94%) and 5-HT_1D receptors (K_i = 0.063–0.50 nM; E_max = 97%), and is among the most potent of the triptan series of drugs.^[2][3][4][5] It is also notable and unique among most of the triptans in being a potent serotonin 5-HT_2A receptor agonist (EC₅₀Tooltip half-maximal effective concentration = 7.94 nM), albeit with about one or two orders of magnitude lower activational potency than at the serotonin 5-HT_1B and 5-HT_1D receptors.^[6]

Chemistry

The predicted log P of donitriptan is 1.32 to 2.2.^[7][8]

History

Donitriptan was being developed in France by bioMérieux-Pierre Fabre and made it to phase II clinical trials in Europe before development was discontinued.^{[9][10][11][2]}