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

The antagonistic potencies of some methoxy-2-aminotetralin derivatives on n icotinic type acetylcholine receptors were compared in rat anococcygeus mus cle and frog rectus abdominis muscle preparations. Stimulation of intrinsic non-adrenergic non-cholinergic (NANC) nerves with nicotine (100 mu mol/l) produced a 65.7 +/- 3.2% relaxation in phenylephrine (1 mu mol/l) precontra cted (2.53 +/- 0.26 g) preparations (n = 17). 2-Aminotetralin derivatives i nhibited the nicotine-induced relaxations in rat anococcygeus muslce in a c oncentration-dependent manner with the following order of potency: BDI-60 > BDI-85 > BDI-51. Preincubation of frog rectus abdominis muscles with the t est compounds caused noncompetitive antagonism as reflected by significant reductions in the maximum contractions obtained with nicotine. The order of potency according to their pD(2)' 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 h as been concluded that doubling the n-propyl residue on the 2-amino moiety causes an increase in the antagonistic potency on nicotonic type acetylchol ine receptors, while shifting of the 8-methoxy residue to the fifth positio n reduces it.