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Effect of piperidine and related alicyclic amines on nicotinic and muscarinic agonist binding sites in the mammalian brain.

The effect of piperidine and related alicyclic amines on central nicotinic and muscarinic cholinoceptors was investigated by measuring specific binding of [3H]nicotine and [3H]cismethyldioxolane (CD) in rat cerebral cortical membranes. Piperidine, pyrrolidine, 4-hydroxypiperidine and piperazine at concentrations of 1 microM-30 mM completed dose-dependently with [3H]nicotine and [3H]CD for the binding sites. Among these compounds, piperidine was the most potent competitor of brain [3H]nicotine binding sites. Piperidine and pyrrolidine showed a greater affinity for [3H]nicotine binding sites in the rat cerebral cortex than of [3H]CD binding sites. In contrast, 4-hydroxypiperidine and piperazine displayed approximately 10 times greater affinity for [3H]CD binding sites. Pipecolic acid had little effect on these cholinoceptor agonist binding sites. The inhibitory effect of brain [3H]nicotine binding by piperidine did not differ between brain regions or during development. In addition, there was little difference in the piperidine-induced inhibition of brain [3H]nicotine binding between species such as rat, mouse, guinea-pig and rabbit. Thus, the present study demonstrates a high affinity of piperidine for nicotinic cholinoceptors in the mammalian brain.