Recently, there has been a rise in the number of amphetamine derivatives that serve as substitutes for controlled substances (e.g. amphetamine and methamphetamine) on the global illegal drug market. These substances are capable of producing rewarding effects similar to their parent drug. In anticipation of the future rise of new and similar psychoactive substances, we designed and synthesized four novel amphetamine derivatives with N-benzyl, N-benzylamphetamine HCl (NBNA) substituent on the amine region, 1,4-dioxane ring, ethylenedioxy-amphetamine HCl (EDA), methyl, para-methylamphetamine HCl (PMEA), and naphthalene, 2-(aminopropyl) naphthalene HCl (2-APN) substituents on the phenyl site. Then, we evaluated their abuse potential in the conditioned place preference (CPP) test in mice and self-administration (SA) test in rats. We also investigated the psychostimulant properties of the novel drugs using the locomotor sensitization test in mice. Moreover, we performed qRT-PCR analyses to explore the effects of the novel drugs on the expression of D1 and D2 dopamine receptor genes in the striatum. NBNA, but not EDA, PMEA, and 2-APN, induced CPP and SA in rodents. None of the test drugs have produced locomotor sensitization. qRT-PCR analyses demonstrated that NBNA increased the expression of striatal D1 dopamine receptor genes. These data indicate that NBNA yields rewarding effects, suggesting potential for abuse. Continual observation for the rise of related substances is thus strongly encouraged.
Amphetamine* ; Animals ; Controlled Substances ; Humans ; Mice ; Parents ; Rats ; Receptors, Dopamine ; Reward ; Rodentia

A diversity of synthetic cathinones has flooded the recreational drug marketplace worldwide. This variety is often a response to legal control actions for one specific compound (e.g. methcathinone) which has resulted in the emergence of closely related replacement. Based on recent trends, the nitrogen atom is one of the sites in the cathinone molecule being explored by designer type modifications. In this study, we designed and synthesized two new synthetic cathinones, (1) α-piperidinopropiophenone (PIPP) and (2) α-piperidinopentiothiophenone (PIVT), which have piperidine ring substituent on their nitrogen atom. Thereafter, we evaluated whether these two compounds have an abuse potential through the conditioned place preference (CPP) in mice and self-administration (SA) in rats. We also investigated whether the substances can induce locomotor sensitization in mice following 7 days daily injection and challenge. qRT-PCR analyses were conducted to determine their effects on dopamine-related genes in the striatum. PIPP (10 and 30 mg/kg) induced CPP in mice, but not PIVT. However, both synthetic cathinones were not self-administered by the rats and did not induce locomotor sensitization in mice. qRT-PCR analyses showed that PIPP, but not PIVT, reduced dopamine transporter gene expression in the striatum. These data indicate that PIPP, but not PIVT, has rewarding effects, which may be attributed to its ability to affect dopamine transporter gene expression. Altogether, this study suggests that PIPP may have abuse potential. Careful monitoring of this type of cathinone and related drugs are advocated.
Animals ; Dopamine Plasma Membrane Transport Proteins ; Gene Expression ; Mice ; Nitrogen ; Rats ; Reward

BACKGROUND: Cardiovascular disease is known as an important predictor of mortality, not only in patients undergoing dialysis treatment but also in those who are starting dialysis treatment. In addition, it is well known that cardiovascular morbidity is about twice higher in diabetic patients. In this study, MIBI and echocardiography were performed in patients starting dialysis treatment, and a comparison of these findings between diabetic (DM) and non-diabetic (Non-DM) patients was done. METHODS: Among the patients diagnosed as end- stage renal disease (ESRD) and started dialysis treatment at Severance Hospital, 77 patients underwent MIBI and echocardiography when they were clinically stable within 4 weeks after the initiation of dialysis. Clinical characteristics, laboratory findings, MIBI and echocardiographic findings of the 77 patients were analyzed. RESULTS: The mean age of the patients was 58.4+/-10.8 years with sex ratio of 1.1: 1. Of the 77 patients, 52 were DM and 25 were Non-DM. There were 30 patients (39.0%) with abnormal findings on MIBI scan, 26 with reVersible and 4 with fixed defects, and 69 patients (89.6%) with left ventricular hypertrophy (LVH) on echocardiography. DM group showed higher prevalence of myocardial perfusion defect than Non-DM group (48.1% vs. 20.0%, p< 0.05). There were no differences in the prevalence of LVH (92.3% vs. 84.0%) and in left ventricular ejection fraction (LVEF) (56.1+/-13.1% vs. 57.5+/-11.8%) between DM and Non-DM groups. LVEF was significantly lower in patients with abnormal findings on MIBI scan than those with normal MIBI finding. CONCLUSION: The majority of ESRD patients starting dialysis treatment accompanied LVH and myocardial perfusion defect was present in many cases especially in diabetic patients. Therefore, early evaluation and treatment of ischemic heart disease are mandatory in diabetic patients starting dialysis treatment for ESRD.
Cardiovascular Diseases ; Diabetes Mellitus ; Dialysis* ; Echocardiography* ; Humans ; Hypertrophy, Left Ventricular ; Kidney Failure, Chronic ; Mortality ; Myocardial Ischemia ; Perfusion ; Prevalence ; Sex Ratio ; Stroke Volume ; Technetium Tc 99m Sestamibi* ; Tomography, Emission-Computed, Single-Photon*