Pharmacological characterizations of the 'legal high' fluorolintane and isomers.
Jason Wallach, Tristan Colestock, Julià Agramunt, Matt D B Claydon, Michael Dybek, Nadine Filemban, Muhammad Chatha, Adam L. Halberstadt, Simon D. Brandt, David Lodge, Zuner A. Bortolotto, Adeboye Adejare
European Journal of Pharmacology August 15, 2019 DOI: 10.1016/j.ejphar.2019.172427 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Rats (hippocampal slices and behavioral experiments) |
| Intervention | fluorolintane |
| Topics | Ketamine |
| Keywords | Diphenidine Fluorolintane Legal high Nmda receptor antagonist |
| Key points | Fluorolintane acts as an NMDA receptor antagonist with high affinity for dopamine transporters, and disrupts sensorimotor gating in rats at a median effective dose of 13.3 mg/kg. |
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 2
- Deaths related to the use of diarylethylamines, with a focus on the United Kingdom: A systematic review and case series report. Journal of Psychopharmacology July 1, 2025
- Is poor dose selection undermining the translational validity of antidepressant research involving animal models? bioRxiv (Cold Spring Harbor Laboratory) November 1, 2025
Cites 18
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- Pharmacological Investigations of the Dissociative ‘Legal Highs’ Diphenidine, Methoxphenidine and Analogues PLoS One June 17, 2016
- First Reported Fatalities Associated with the 'Research Chemical' 2-Methoxydiphenidine Journal of Analytical Toxicology February 19, 2015
- Effects of the new psychoactive substances diclofensine, diphenidine, and methoxphenidine on monoaminergic systems European Journal of Pharmacology December 8, 2017
- Test purchase, synthesis, and characterization of 2‐methoxydiphenidine (MXP) and differentiation from its meta‐ and para‐substituted isomers Drug Testing and Analysis April 15, 2015
and 13 more in the library