SB-656104A (SB-656104-A) is a potent, selective 5-HT7 receptor antagonist, potently inhibits [3H]-SB-269970 binding to the human cloned 5-HT7(a) (pKi=8.7) and 5-HT7(b) (pKi=8.5) receptor variants and the rat native receptor (pKi=8.8).
SB-656104A (SB-656104-A) displays at least 30-fold selectivity for the human 5-HT7(a) receptor versus other human cloned 5-HT receptors apart from the 5-HT1D receptor (∼10-fold selective).
SB-656104-A antagonised competitively the 5-carboxamidotryptamine (5-CT)-induced accumulation of cyclic AMP in h5-HT7(a)/HEK293 cells with a pA2 of 8.5.
SB-656104-A produced a significant reversal of the 5-CT-induced hypothermic effect in guinea pigs, a pharmacodynamic model of 5-HT7 receptor interaction in vivo (ED50 2 mg kg−1).
SB-656104A (SB-656104-A) significantly increased the latency to onset of rapid eye movement (REM) sleep at 30 mg kg−1 i.p. (+93%) and reduced the total amount of REM sleep at 10 and 30 mg kg−1 i.p.