<p>P.1.g.036 <a href="/tags/Monoamine_transporter/" rel="tag">Monoamine transporter</a> and <a href="/tags/Receptor_(biochemistry)/" rel="tag">receptor</a> interaction profiles of novel <a href="/tags/Phenethylamine/" rel="tag">phenethylamine</a> derivatives Dino Luethi1, Philine J Kaeser1, Anna Rickli1, Marius C Hoener2, Matthias E Liechti1 </p><p>1Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland 2Neuroscience Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland </p><p>Introduction Methods Novel psychoactive <a href="/tags/Phenethylamine/" rel="tag">phenethylamines</a> constantly emerge on the illicit HEK cells overexpressing human <a href="/tags/Serotonin/" rel="tag">serotonin</a>- (hSERT) <a href="/tags/Dopamine/" rel="tag">dopamine</a>- drug market and are often sold as “legal highs” over the Internet as (hDAT), or <a href="/tags/Norepinephrine/" rel="tag">norepinephrine</a>- (hNET) re-uptake transporters were used alternatives to illegal drugs. In the current study, we investigated the in for uptake and release experiments. To determine the potency of drugs 3 vitro pharmacological mechanism of action of the novel phenethylamine to inhibit monoamine-uptake, we assessed uptake of [ H]-labelled monoamines in presence of different drug concentrations. For the derivatives 5-(2-aminopropyl)indole (5-IT), 3,4- release assay, we pre-loaded the cells with the respective [3H]- dimethylmethcathinone (3,4-DMMC), 4-methylamphetamine (4-MA), 3- monoamines, washed, and induced release with the addition of the methylmethcathinone (3-MMC), and N-methyl-2-aminoindane (N- drugs at a single high concentration. methyl-2-AI). </p><p>Figure 1. Structures of novel phenethylamine derivatives. Results </p><p>Figure 2. Monoamine transporter inhibition. Figure 3. Drug induced monoamine release.</p><p>Conclusion The authors report no conflict of interest. All substances strongly inhibited the NET as it is known for classic <a href="/tags/Amphetamine/" rel="tag">amphetamines</a>, suggesting Contact: [email protected] marked sympathomimetic properties. 3,4-DMMC and 4-MA inhibited the SERT more strongly [email protected] than the DAT, thereby exhibiting pharmacological properties similar to 3,4- methylenedioxymethamphetamine (MDMA) and suggesting similar empathogenic effects. All substances were releasers of monoamines. However, 5-IT caused efflux of DA and 5-HT but not NE and N-methyl-2-AI caused efflux of NE only.</p>