Antinicotinic activity of some 2-aminotetralin derivatives. A structure-activity relationship study

The antagonistic potencies of some methoxy-2-aminotetralin derivatives on nicotinic type acetylcholine receptors were compared in rat anococcygeus muscle and frog rectus abdominis muscle preparations. Stimulation of intrinsic non-adrenergic non-cholinergic (NANC) nerves with nicotine (100 mumol/l) produced a 65.7 +/- 3.2% relaxation in phenylephrine (1 mumol/l) precontracted (2.53 +/- 0.20 g) preparations (n = 17). 2-Aminotetralin derivatives inhibited the nicotine-induced relaxations in rat anococcygeus muscle in a concentration-dependent manner with the following order of potency: BDI-60 > BDI-85 > BDI-51. Preincubation of frog rectus abdominis muscles with the test compounds caused noncompetitive antagonism as reflected by significant reductions in the maximum contractions obtained with nicotine. The order of potency according to their pD2' values was BDI-60 > BDI-85 > BDI-51. All three compounds possess antagonistic action with the same order of potency on both neuronal and muscular type nicotinic acetylcholine receptors. It has been concluded that doubling the n-propyl residue on the 2-amino moiety causes an increase in the antagonistic potency on nicotonic type acetylcholine receptors, while shifting of the 8-methoxy residue to the fifth position reduces it.