1-Benzenesulfonyl-5-methoxy-N, N-dimethyltryptamine (3; Ki= 2.3 nM) is a 5-HT6 receptor antagonist; removal of the 5-methoxy group (ie, 6; Ki= 4.1 nM) has little impact on receptor affinity. In the present study, it is shown that the aminomethyl portion of 6 can be shortened to gramine analogue 10a (Ki= 3.1 nM); a related skatole derivative 11b (Ki= 12 nM) also binds with high affinity indicating that the aminoethyl portion of the tryptamines is not ...