{'fraction_non_alphanumeric': 0.05837711617046118, 'fraction_numerical': 0.04319906596614127, 'mean_word_length': 5.443609022556391, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
A Trifluoromethylphenyl Piperazine Derivative with High Affinity for 5‐Hydroxytryptamine‐1A Sites in Rat Brain

Abstract: The inhibition of [3H]5‐hydroxytryptamine ([3H]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 [3H]5‐HT binding in cortex was consistent with displacement from two sites with dissociation constants (KD) of 24 nM (5‐HT‐1A site) and 19 μM (5‐HT‐1B site) for spiperone. BrAcTFMPP also discriminated two subpopulations of [3H]5‐HT binding sites with dissociation constants of 0.5 nM and 146 nM for the compound. The proportion of high‐affinity sites for each compound represented about 35% of the specific [3H]5‐HT binding. In the presence of 1 μMspiperone, a concentration that saturates the 5‐HT‐1A sites while having a minimal effect on 5‐HT‐1B sites, BrAcTFMPP displaced [3H]5‐HT from a single site with a KD for BrAcTFMPP of 145 nM. The inhibition of [3H]5‐HT binding by spiperone in the presence of 30 nM BrAcTFMPP was best fit by a single‐site model with a KD of 21 μM for spiperone. In corpus striatum, 5‐HT‐1A sites, as defined with spiperone, represented 15% of the specific [3H]5‐HT binding and 30 nM BrAcTFMPP also blocked about 15% of the binding. A significant difference between spiperone and BrAcTFMPP was their affinity for 5‐HT‐2 receptors. BrAcTFMPP (KD= 41 nM) had an 80‐fold lower affinity for these sites than spiperone (KD= 0.5 nM). Thus, BrAcTFMPP and spiperone discriminate the same two subpopulations of [3H]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.