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Pharmacological characterizations of the 'legal high' fluorolintane and isomers

Wallach, J, Colestock, T, Agramunt, J, Claydon, MDB, Dybek, M, Filemban, N, Chatha, M, Halberstadt, AL, Brandt, SD, Lodge, D, Bortolotto, ZA and Adejare, A (2019) Pharmacological characterizations of the 'legal high' fluorolintane and isomers. Behavioural Processes. ISSN 0376-6357

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1,2-Diarylethylamines represent a class of molecules that have shown potential in pain, epilepsy, neurodegenerative disease and depression. Examples include lefetamine, remacemide, and lanicemine. Recently, several 1,2-diarylethylamines including the dissociatives diphenidine, methoxphenidine and ephenidine as well as the opioid MT-45, have appeared as ‘research chemicals’ or ‘legal highs’. Due to their rapid emergence little is known about their pharmacology. One of these, 1-[1-(2-fluorophenyl)-2-phenylethyl]pyrrolidine (fluorolintane, 2-F-DPPy), is available for purchase with purported dissociative effects meant to mimic phencyclidine (PCP) and ketamine. To better understand this emerging class, pharmacological investigations were undertaken for the first time on fluorolintane and its five aryl-fluorine-substituted isomers. In vitro binding studies revealed high N-methyl-D-aspartate (NMDA) receptor affinity (Ki = 87.92 nM) and off-target affinities at several sites including norepinephrine (NET), serotonin (SERT) and dopamine (DAT) transporters, and sigma receptors. High affinities for DAT were observed, which were typically greater than NMDA receptor affinities. Additional functional and behavioral experiments show fluorolintane inhibited NMDA receptor-induced field excitatory postsynaptic potentials in rat hippocampal slices and inhibited long-term potentiation induced by theta-burst stimulation in rat hippocampal slices with potencies consistent with its NMDA receptor antagonism. Finally fluorolintane significantly inhibited prepulse inhibition in rats, a measure of sensorimotor gating, with a median effective dose (ED50) of 13.3 mg/kg. These findings are consistent with anecdotal reports of dissociative effects of fluorolintane in humans.

Item Type: Article
Uncontrolled Keywords: 0801 Artificial Intelligence and Image Processing, 1701 Psychology, 1702 Cognitive Sciences, 1115 Pharmacology and Pharmaceutical Sciences
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
Date Deposited: 05 Jun 2019 10:33
Last Modified: 04 Sep 2021 09:19
DOI or ID number: 10.1016/j.ejphar.2019.172427
URI: https://researchonline.ljmu.ac.uk/id/eprint/10821
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