Pharmacological Characterization of 4-Methylthioamphetamine Derivatives

Abstract

Amphetamine derivatives have been used in a wide variety of pathologies because of their pharmacological properties as psychostimulants, entactogens, anorectics, and antidepressants. However, adverse cardiovascular effects (sympathomimetics) and substance abuse problems (psychotropic and hallucinogenic effects) have limited their use. 4-Methylthioamphetamine (MTA) is an amphetamine derivative that has shown to inhibit monoamine uptake and monoamine oxidase. However, the pharmacological characterization (neurochemical, behavioral, and safety) of its derivatives 4-ethylthioamphetamine (ETA) and 4-methylthio-phenil-2-butanamine (MT-But) have not been studied. In the current experiments, we show that ETA and MT-But do not increase locomotor activity and conditioned place preference with respect to MTA. At the neurochemical level, ETA and MT-But do not increase in vivo DA release in striatum, but ETA and MT-But affect the nucleus accumbens bioaccumulation of DA and DOPAC. Regarding cardiovascular effects, the administration of MTA and ETA increased the mean arterial pressure and only ETA significantly increases the heart rate. Our results show that the pharmacological and safety profiles of MTA are modulated by changing the methyl-thio group or the methyl group of the aminoethyl chain.

Effects of Early Life Exposure to Sex Hormones on Neurochemical and Behavioral Responses to Psychostimulants in Adulthood: Implications in Drug Addiction

“…FSCV experiments were performed on anesthetized rats, following a previously published protocol [ 38 ]. Briefly, 3 electrodes (working, reference and bipolar stimulating electrode) were implanted using the coordinates from the Rat Brain Atlas.…”

Early-Life Exposure to Non-Absorbable Broad-Spectrum Antibiotics Affects the Dopamine Mesocorticolimbic Pathway of Adult Rats in a Sex-Dependent Manner

“…NAcc and VTA were micro-dissected at 4 °C using a brain matrix (model 68711, RWD Life Science, Shenzhen, P.R. China) and micro-punch (model 15076; diameter 2.0 mm, Harris Uni-Core, Ted-Pella Inc., Redding, CA, United States) as described previously ( Bonansco et al, 2018 ; Guajardo et al, 2020 ). Briefly, NAcc and VTA were weighed on an analytical balance (model JK-180, Chyo balance corp, Tokyo, Japan) and homogenized in 400 μl of 0.2 N perchloric acid using a sonicator (model XL2005, Microson Ultrasonic Cell Disruptor, Heat Systems, Farmingdale, NY, United States).…”