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A Trifluoromethylphenyl Piperazine Derivative with High Affinity for 5‐Hydroxytryptamine‐1A Sites in Rat Brain
Author(s) -
Ransom Richard W.,
Asarch Kenneth B.,
Shih Jean C.
Publication year - 1985
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.1471-4159.1985.tb12897.x
Subject(s) - spiperone , dissociation constant , binding site , chemistry , 5 ht receptor , stereochemistry , striatum , piperazine , receptor , serotonin , biology , endocrinology , biochemistry , dopamine , organic chemistry
The inhibition of [ 3 H]5‐hydroxytryptamine ([ 3 H]5‐HT) binding in rat brain by 1‐[2‐(3‐bromoacetamidophenyl)ethyl]‐4‐(3‐trifluoromethylphenyl) piperazine (BrAcTFMPP) and that by spiperone were compared. Spiperone inhibition of [ 3 H]5‐HT binding in cortex was consistent with displacement from two sites with dissociation constants ( K D ) of 24 n M (5‐HT‐1A site) and 19 μ M (5‐HT‐1B site) for spiperone. BrAcTFMPP also discriminated two subpopulations of [ 3 H]5‐HT binding sites with dissociation constants of 0.5 n M and 146 n M for the compound. The proportion of high‐affinity sites for each compound represented about 35% of the specific [ 3 H]5‐HT binding. In the presence of 1 μ M spiperone, a concentration that saturates the 5‐HT‐1A sites while having a minimal effect on 5‐HT‐1B sites, BrAcTFMPP displaced [ 3 H]5‐HT from a single site with a K D for BrAcTFMPP of 145 n M. The inhibition of [ 3 H]5‐HT binding by spiperone in the presence of 30 n M BrAcTFMPP was best fit by a single‐site model with a K D of 21 μ M for spiperone. In corpus striatum, 5‐HT‐1A sites, as defined with spiperone, represented 15% of the specific [ 3 H]5‐HT binding and 30 n M BrAcTFMPP also blocked about 15% of the binding. A significant difference between spiperone and BrAcTFMPP was their affinity for 5‐HT‐2 receptors. BrAcTFMPP ( K D = 41 n M ) had an 80‐fold lower affinity for these sites than spiperone ( K D = 0.5 n M ). Thus, BrAcTFMPP and spiperone discriminate the same two subpopulations of [ 3 H]5‐HT binding sites and BrAcTFMPP displays a high affinity and a selectivity for 5‐HT‐1A sites versus both 5‐HT‐1B and 5‐HT‐2 sites.