Receptor binding characteristics of a 3H-labeled azetidine analogue of nicotine.

A new radioligand, (+/-)-[3H]-1-methyl-2-(3-pyridyl)-azetidine, which is an analogue of nicotine, has been used to investigate the binding characteristics of the nicotine receptor in rat brain membranes. By Scatchard analysis, the azetidine analogue yielded a curvilinear plot with Kd values of 7 X 10(-11) and 1.7 X 10(-9) M and Bmax values of 0.3 X 10(-14) and 2.5 X 10(-14) mol/mg protein respectively. Thermodynamic analyses yielded negative free enthalpy values for both sites, a decrease in the Bmax of only the lower affinity site, and no effect on either Kd. The psychotropic potency (prostration in rats following intraventricular injection) of the azetidine analogue was about 5-fold greater than (-)-nicotine, being among the greatest of any known nicotine analogues tested to date. Since only the higher affinity Kd differed from that of (-)-nicotine, 3-fold greater, the psychotropic potency appears to be correlated with the higher affinity site. Insofar as [3H]methylcarbamylcholine, a nicotinic ligand resembling acetylcholine, exhibits a linear Scatchard with a Kd of 1 X 10(-9) M, the higher affinity site appears to be characteristic of nicotine analogues.