[3H]1‐[2‐(4‐Aminophenyl)Ethyl]‐4‐(3‐Trifluoromethylphenyl)Piperazine: A Selective Radioligand for 5‐HT1A Receptors in Rat Brain

doi:10.1111/j.1471-4159.1986.tb12926.x

Paper

[3H]1‐[2‐(4‐Aminophenyl)Ethyl]‐4‐(3‐Trifluoromethylphenyl)Piperazine: A Selective Radioligand for 5‐HT1A Receptors in Rat Brain

Published Jan 1, 1986 · R. Ransom, K. Asarch, J. Shih

Journal of Neurochemistry

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52

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Abstract

Abstract: 1‐[2‐(4‐Aminophenyl)ethyl]‐4‐(3‐trifluoromethylphenyl)piperazine (PAPP) inhibits [3H]5‐hydroxytryptamine (5‐HT, serotonin) binding to 5‐HT1A and 5‐HT1B sites in rat brain with apparent equilibrium dissociation constants (KD) of 2.9 and 328 nM, respectively. [3H]PAPP was synthesized, its binding to central serotonin receptors was examined, and its potential usefulness as a 5‐HT1A receptor radioligand was evaluated. With either 10 μM 5‐HT or 1 μM 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin to define nonspecific binding, [3H]PAPP bound to a single class of sites in rat cortical membranes with a KD of 1.6 nM and a maximal binding density (Bmax) of 162 fmol/mg of protein. d‐Lysergic acid diethylamide and 5‐HT, two nonselective inhibitors of [3H]5‐HT binding, displaced 1 nM [3H]PAPP with a potency that matched their affinity for 5‐HT1 receptors. Spiperone and 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin, two compounds that discriminate [3H]5‐HT binding to 5‐HT1A and 5‐HT1B sites, inhibited [3H]PAPP binding in accordance with their much higher affinities for the 5‐HT1A receptor subtype. Furthermore, the ability of N‐(m‐trifluoromethylphenyl)piperazine and ketanserin to inhibit [3H]PAPP binding reflected their low affinities for the 5‐HT1A receptor. Several nonserotonergic compounds were also found to be relatively poor displacers of [3H]PAPP binding. The regional distribution of serotonin‐sensitive [3H]PAPP sites correlated with the densities of 5‐HT1A receptors in the cortex, hippocampus, corpus striatum, and cerebellum of the rat. These results indicate that [3H]PAPP binds selectively and with high affinity to 5‐HT1A receptor sites in rat brain.

In Vitro Study

Study Snapshot

[3H]PAPP selectively and with high affinity binds to 5HT1A receptor sites in rat brain, suggesting its potential usefulness as a 5HT1A receptor radioligand.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

[3H]1‐[2‐(4‐Aminophenyl)Ethyl]‐4‐(3‐Trifluoromethylphenyl)Piperazine: A Selective Radioligand for 5‐HT1A Receptors in Rat Brain

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References

5-HT-1a and 5-HT-1b selectivity of two phenylpiperazine derivatives: evidence for 5-HT-1b heterogeneity.

TFMPP shows 30 fold selectivity for 5-HT-1b subtype, while p-NH2-PE-TFMPP exhibits 110 fold selectivity for 5-HT-la sites, with no subtype discrimination within 5-HT-1b binding sites.

A Trifluoromethylphenyl Piperazine Derivative with High Affinity for 5‐Hydroxytryptamine‐1A Sites in Rat Brain

BrAcTFMPP has a high affinity and selectivity for 5HT1A sites in rat brain, with a lower affinity for 5HT1B and 5HT2 sites.

Determination of selective and nonselective compounds for the 5-HT 1A and 5-HT 1B receptor subtypes in rat frontal cortex.

Selective compounds like 1-(m-trifluoromethylphenyl) piperazine and spiperone show over 100-fold selectivity for one of the two 5-HT1 receptor subtypes in rat frontal cortex.

The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)tetralin in the rat.

8-OH-DPAT's behavioral effects in rats may reflect the consequences of stimulation of the putative 5-HT 1A receptor.

Biochemical evidence for the 5-HT agonist properties of PAT (8-hydroxy-2-(di-n-propylamino)tetralin) in the rat brain.

PAT is a potent 5-HT agonist acting on both post- and presynaptic receptors in the rat brain.

Citations

Development of selective agents targeting serotonin 5HT1A receptors with subnanomolar activities based on a coumarin core.

Six new coumarin derivatives show high affinity for serotonin 5HT1A receptors and good selectivity against 5-HT2A receptors, offering potential therapeutic applications.

Gd(III)‐DO3A‐SBMPP:An Effort to Develop the MRI Contrast Agent with Enhanced Relaxivity

Gd-DO3A-SBMPP shows enhanced relaxivity and potential for use in MRI contrast agents, with good biocompatibility and functionalities in targeting brain regions.

Synthesis and structure–activity relationships of new arylpiperazines: para substitution with electron-withdrawing groups decrease binding to 5-HT1A and D2A receptors

Electron-withdrawing phenyl ring substituents in para positions of arylpiperazines significantly reduce binding to 5-HT1A and D2A receptors, with binding at 5HT1A influenced by the bulk of substituents and binding at D2A by their electronic properties.

Preclinical pharmacology of B-20991, a 5-HT1A receptor agonist with anxiolytic activity.

B-20991 is a 5-HT1A receptor agonist with anxiolytic activity, exhibiting dose-related increases in social interaction and light/dark box behavioral scores.

Role of hippocampal serotonergic neurons in ischemic neuronal death

Intrahippocampal treatment with ZD-211 or buspirone can protect neuronal damage following transient ischemia in gerbils, with enhanced activity of the 5-HT nervous system in the hippocampus.