TY - JOUR T1 - <strong>Neurochemical and cardiovascular effects of 4-chloro ring-substituted synthetic cathinones in rats</strong> JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.122.001478 SP - JPET-AR-2022-001478 AU - Michael R Chojnacki AU - Eric B. Thorndike AU - John S. Partilla AU - Kenner C. Rice AU - Charles W. Schindler AU - Michael H Baumann Y1 - 2023/01/01 UR - http://jpet.aspetjournals.org/content/early/2023/01/20/jpet.122.001478.abstract N2 - Synthetic cathinones are a class of new psychoactive substances that display psychomotor stimulant properties, and novel cathinone analogs continue to emerge in illicit drug markets worldwide. The aim of the present study was to characterize the pharmacology of 4-chloro ring-substituted cathinones that are appearing in illicit drug markets, as compared to the effects of 4-methylmethcathinone (mephedrone). Synaptosomes were prepared from rat caudate for dopamine transporter (DAT) assays, or from whole brain minus caudate and cerebellum for norepinephrine transporter (NET) and serotonin transporter (SERT) assays. Findings from transporter uptake inhibition and release assays showed that mephedrone and 4-chloromethcathinone (4-CMC) function as substrates at DAT, NET, and SERT, with similar potency at all three transporters. In contrast, 4-chloro-a-pyrrolidinopropiophenone (4-CaPPP) was an uptake inhibitor at DAT and NET, with similar potency at each site, but had little activity at SERT. 4-Chloroethcathinone (4-CEC) was a low potency uptake inhibitor at DAT and NET but a substrate at SERT. In rats implanted with telemetry transmitters, mephedrone and 4-CMC increased blood pressure, heart rate, and locomotor activity to a similar extent. 4-CEC and 4-CaPPP were less potent at increasing blood pressure and had modest stimulatory effects on heart rate and activity. 4-CMC also transiently decreased temperature at the highest dose tested. All three 4-chloro ring-substituted cathinones are biologically active, but only 4-CMC has potency comparable to mephedrone. Collectively, our findings suggest that 4-CMC and other 4-chloro cathinones may have abuse potential and adverse effects in humans that are analogous to those associated with mephedrone. Significance Statement The 4-chloro ring-substituted cathinones all produced significant cardiovascular effects, with 4-CMC showing potency similar to mephedrone. All the drugs are likely to be abused given their effects at the DAT, particularly 4-CMC. ER -