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Pharmacological characterizations of the 'legal high' fluorolintane and isomers

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Pharmacological characterizations of the 'legal high' fluorolintane and isomers. / Wallach, Jason; Colestock, Tristan; Agramunt, Julià; Claydon, Matt; Dybek, Michael; Filemban, Nathalie; Chatha, Muhammad; Halberstadt, Adam L.; Halberstadt, Adam L.; Brandt, Simon; Lodge, David; Bortolotto, Zuner A; Adejare, Adeboye.

In: European Journal of Pharmacology, Vol. 857, 172427, 15.08.2019.

Research output: Contribution to journalArticle

Harvard

Wallach, J, Colestock, T, Agramunt, J, Claydon, M, Dybek, M, Filemban, N, Chatha, M, Halberstadt, AL, Halberstadt, AL, Brandt, S, Lodge, D, Bortolotto, ZA & Adejare, A 2019, 'Pharmacological characterizations of the 'legal high' fluorolintane and isomers', European Journal of Pharmacology, vol. 857, 172427. https://doi.org/10.1016/j.ejphar.2019.172427

APA

Wallach, J., Colestock, T., Agramunt, J., Claydon, M., Dybek, M., Filemban, N., ... Adejare, A. (2019). Pharmacological characterizations of the 'legal high' fluorolintane and isomers. European Journal of Pharmacology, 857, [172427]. https://doi.org/10.1016/j.ejphar.2019.172427

Vancouver

Wallach J, Colestock T, Agramunt J, Claydon M, Dybek M, Filemban N et al. Pharmacological characterizations of the 'legal high' fluorolintane and isomers. European Journal of Pharmacology. 2019 Aug 15;857. 172427. https://doi.org/10.1016/j.ejphar.2019.172427

Author

Wallach, Jason ; Colestock, Tristan ; Agramunt, Julià ; Claydon, Matt ; Dybek, Michael ; Filemban, Nathalie ; Chatha, Muhammad ; Halberstadt, Adam L. ; Halberstadt, Adam L. ; Brandt, Simon ; Lodge, David ; Bortolotto, Zuner A ; Adejare, Adeboye. / Pharmacological characterizations of the 'legal high' fluorolintane and isomers. In: European Journal of Pharmacology. 2019 ; Vol. 857.

Bibtex

@article{50b9fafa8af841339393f23607996646,
title = "Pharmacological characterizations of the 'legal high' fluorolintane and isomers",
abstract = "1,2-Diarylethylamines represent a class of molecules that have shown potential in the treatment of 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 recent 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 intended to resemble 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 affinity for N-methyl-D-aspartate (NMDA) receptors with fluorolintane (Ki = 87.92 nM) with lesser affinities for related compounds. Additional affinities were seen for all compounds at several sites including norepinephrine (NET), serotonin (SERT) and dopamine (DAT) transporters, and sigma receptors. Notably high affinities at DAT were observed, which were in most cases 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 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.",
keywords = "NMDA receptor antagonist, legal high, fluorolintane, diphenidine, new psychoactive substance, ketamine.",
author = "Jason Wallach and Tristan Colestock and Juli{\`a} Agramunt and Matt Claydon and Michael Dybek and Nathalie Filemban and Muhammad Chatha and Halberstadt, {Adam L.} and Halberstadt, {Adam L.} and Simon Brandt and David Lodge and Bortolotto, {Zuner A} and Adeboye Adejare",
year = "2019",
month = "8",
day = "15",
doi = "10.1016/j.ejphar.2019.172427",
language = "English",
volume = "857",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "North-Holland Publishing Company",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Pharmacological characterizations of the 'legal high' fluorolintane and isomers

AU - Wallach, Jason

AU - Colestock, Tristan

AU - Agramunt, Julià

AU - Claydon, Matt

AU - Dybek, Michael

AU - Filemban, Nathalie

AU - Chatha, Muhammad

AU - Halberstadt, Adam L.

AU - Halberstadt, Adam L.

AU - Brandt, Simon

AU - Lodge, David

AU - Bortolotto, Zuner A

AU - Adejare, Adeboye

PY - 2019/8/15

Y1 - 2019/8/15

N2 - 1,2-Diarylethylamines represent a class of molecules that have shown potential in the treatment of 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 recent 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 intended to resemble 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 affinity for N-methyl-D-aspartate (NMDA) receptors with fluorolintane (Ki = 87.92 nM) with lesser affinities for related compounds. Additional affinities were seen for all compounds at several sites including norepinephrine (NET), serotonin (SERT) and dopamine (DAT) transporters, and sigma receptors. Notably high affinities at DAT were observed, which were in most cases 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 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.

AB - 1,2-Diarylethylamines represent a class of molecules that have shown potential in the treatment of 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 recent 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 intended to resemble 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 affinity for N-methyl-D-aspartate (NMDA) receptors with fluorolintane (Ki = 87.92 nM) with lesser affinities for related compounds. Additional affinities were seen for all compounds at several sites including norepinephrine (NET), serotonin (SERT) and dopamine (DAT) transporters, and sigma receptors. Notably high affinities at DAT were observed, which were in most cases 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 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.

KW - NMDA receptor antagonist

KW - legal high

KW - fluorolintane

KW - diphenidine

KW - new psychoactive substance

KW - ketamine.

UR - http://www.scopus.com/inward/record.url?scp=85066828661&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2019.172427

DO - 10.1016/j.ejphar.2019.172427

M3 - Article

VL - 857

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

M1 - 172427

ER -