Originator
WY-50324 ,Centre de Recherche
Pierre Fabre
Uses
Adatanserin hydrochloride is a high affinity, selective and partial agonist for the 5-HT1A receptor with a Ki of 1 nM. Adatanserin hydrochloride is a moderate affinity 5-HT2 receptor antagonist with a Ki of 73 nM. Adatanserin hydrochloride shows significant anxiolytic and antidepressant activity in an animal conflict model[1][2].
Manufacturing Process
To a stirred solution of [4-(2-pyrimidinyl)piperazino]ethylamine (2.0 g, 0.01
mol) in 50 ml of methylene chloride, adamantane-1-carboxylic acid chloride
(3.6 g, 0.018 mol) and triethylamine (2.9 g, 0.015 mol) were added. Stirring
was continued at room temperature overnight. The methylene chloride
solution was washed with water, dried over anhydrous sodium sulfate and
evaporated under reduced pressure. The remaining residue was subjected to
preparative HPLC. The residue was dissolved in ethyl acetate (10 ml) and
subjected to flash chromatography using a 9 inch column of silica gel and
ethyl acetate as the eluent. The N-[2-[4-(2-pyrimidinyl)-1-
piperazinyl]ethyl]tricyclo[3.3.1.1(3,7)]
decane-1-carboxamide was separated.
In practice it is usually used as hydrochloride.
Therapeutic Function
Anxiolyticá Antidepressant
References
[1] M A Abou-Gharbia, et al. Synthesis and SAR of adatanserin: novel adamantyl aryl- and heteroarylpiperazines with dual serotonin 5-HT(1A) and 5-HT(2) activity as potential anxiolytic and antidepressant agents. DOI:
10.1021/jm9806704[2] A Singh, et al. Antidepressant-like activity of compounds with varying efficacy at 5-HT1A receptors. Neuropharmacology. 1993 Apr;32(4):331-40. DOI:
10.1016/0028-3908(93)90153-t
