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[ 3 H]1‐[2‐(4‐Aminophenyl)Ethyl]‐4‐(3‐Trifluoromethylphenyl)Piperazine: A Selective Radioligand for 5‐HT 1A Receptors in Rat Brain
Author(s) -
Ransom Richard W.,
Asarch Kenneth B.,
Shih Jean C.
Publication year - 1986
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1986.tb12926.x
Subject(s) - radioligand , receptor , chemistry , 5 ht receptor , radioligand assay , dissociation constant , spiperone , binding site , ketanserin , stereochemistry , serotonin , piperazine , binding potential , biochemistry , organic chemistry
1‐[2‐(4‐Aminophenyl)ethyl]‐4‐(3‐trifluoromethylphenyl)piperazine (PAPP) inhibits [ 3 H]5‐hydroxytryptamine (5‐HT, serotonin) binding to 5‐HT 1A and 5‐HT 1B sites in rat brain with apparent equilibrium dissociation constants ( K D ) of 2.9 and 328 n M , respectively. [ 3 H]PAPP was synthesized, its binding to central serotonin receptors was examined, and its potential usefulness as a 5‐HT 1A receptor radioligand was evaluated. With either 10 μ M 5‐HT or 1 μ M 8‐hydroxy‐2‐(di‐ n ‐propylamino)tetralin to define nonspecific binding, [ 3 H]PAPP bound to a single class of sites in rat cortical membranes with a K D of 1.6 n M and a maximal binding density (B max ) of 162 fmol/mg of protein. d ‐Lysergic acid diethylamide and 5‐HT, two nonselective inhibitors of [ 3 H]5‐HT binding, displaced 1 n M [ 3 H]PAPP with a potency that matched their affinity for 5‐HT 1 receptors. Spiperone and 8‐hydroxy‐2‐(di‐ n ‐propylamino)tetralin, two compounds that discriminate [ 3 H]5‐HT binding to 5‐HT 1A and 5‐HT 1B sites, inhibited [ 3 H]PAPP binding in accordance with their much higher affinities for the 5‐HT 1A receptor subtype. Furthermore, the ability of N‐(m ‐trifluoromethylphenyl)piperazine and ketanserin to inhibit [ 3 H]PAPP binding reflected their low affinities for the 5‐HT 1A receptor. Several nonserotonergic compounds were also found to be relatively poor displacers of [ 3 H]PAPP binding. The regional distribution of serotonin‐sensitive [ 3 H]PAPP sites correlated with the densities of 5‐HT 1A receptors in the cortex, hippocampus, corpus striatum, and cerebellum of the rat. These results indicate that [ 3 H]PAPP binds selectively and with high affinity to 5‐HT 1A receptor sites in rat brain.