From street to lab: in vitro hepatotoxicity of buphedrone, butylone and 3,4-DMMC.

Synthetic cathinones are among the most popular new psychoactive substances, being abused for their stimulant properties, which are similar to those of amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Considering that the liver is a likely target for cathinones-induced toxicity, and for their metabolic activation/detoxification, we aimed to determine the hepatotoxicity of three commonly abused synthetic cathinones: butylone, α-methylamino-butyrophenone (buphedrone) and 3,4-dimethylmethcathinone (3,4-DMMC). We characterized their cytotoxic profile in primary rat hepatocytes (PRH) and in the HepaRG and HepG2 cell lines. PRH was the most sensitive cell model, showing the lowest EC50 values for all three substances (0.158 mM for 3,4-DMMC; 1.21 mM for butylone; 1.57 mM for buphedrone). Co-exposure of PRH to the synthetic cathinones and CYP450 inhibitors (selective and non-selective) proved that hepatic metabolism reduced the toxicity of buphedrone but increased that of butylone and 3,4-DMMC. All compounds were able to increase oxidative stress, disrupting mitochondrial homeostasis and inducing apoptotic and necrotic features, while also increasing the occurrence of acidic vesicular organelles in PRH, compatible with autophagic activation. In conclusion, butylone, buphedrone and 3,4-DMMC have hepatotoxic potential, and their toxicity lies in the interference with a number of homeostatic processes, while being influenced by their metabolic fate.

Development and Quality evaluation of sustained release pellets of eperisone HCl.

The objective was to develop eperisone HCl sustained-release pellets through extrusion spheronization technique and to determine the influence of different hydrophobic (polymeric based and wax-based) and hydrophilic (polymeric based) matrix former on the release of eperisone HCl (BCS class I drug) and on pellet sphericity. The pellet formulations consisted of different hydrophobic and hydrophilic matrix formers like HPMC K4M (10-20%) HPMC K15M (10%), EC (7cps) (10-20%), Carnauba wax (10-20%), Compritol ATO 888 (10-20%), Glyceryl monostearate (10%), lactose and microcrystalline cellulose. The initial burst release of the drug from matrix pellet formulations was effectively controlled by coating with 5% EC (ethylcellulose) dispersion. The dissolution profile and drug release kinetics of coated pellet formulations were determined at both acidic and basic pH medium. SEM (Scanning electron microscope) technique was used to determine the surface morphology and cross-section of F5 and F7 pellet formulation. The mechanism of drug release of coated formulation followed non-Fickian diffusion. FTIR spectroscopy was conducted and no drug and excipients interaction was observed. The results had shown that optimized coated formulation was F5 and F7 which effectively extend the drug release for 12 hours.

Subacute administration of both methcathinone and manganese causes basal ganglia damage in mice resembling that in methcathinone abusers.

An irreversible extrapyramidal syndrome occurs in man after intravenous abuse of "homemade" methcathinone (ephedrone, Mcat) that is contaminated with manganese (Mn) and is accompanied by altered basal ganglia function. Both Mcat and Mn can cause alterations in nigrostriatal function but it remains unknown whether the effects of the 'homemade' drug seen in man are due to Mcat or to Mn or to a combination of both. To determine how toxicity occurs, we have investigated the effects of 4-week intraperitoneal administration of Mn (30 mg/kg t.i.d) and Mcat (100 mg/kg t.i.d.) given alone, on the nigrostriatal function in male C57BL6 mice. The effects were compared to those of the 'homemade' mixture which contained about 7 mg/kg of Mn and 100 mg/kg of Mcat. Motor function, nigral dopaminergic cell number and markers of pre- and postsynaptic dopaminergic neuronal integrity including SPECT analysis were assessed. All three treatments had similar effects on motor behavior and neuronal markers. All decreased motor activity and induced tyrosine hydroxylase positive cell loss in the substantia nigra. All reduced 123I-epidepride binding to D2 receptors in the striatum. Vesicular monoamine transporter 2 (VMAT2) binding was not altered by any drug treatment. However, Mcat treatment alone decreased levels of the dopamine transporter (DAT) and Mn alone reduced GAD immunoreactivity in the striatum. These data suggest that both Mcat and Mn alone could contribute to the neuronal damage caused by the 'homemade' mixture but that both produce additional changes that contribute to the extrapyramidal syndrome seen in man.

Improving mucosal anesthesia for awake endotracheal intubation with a novel method: a prospective, assessor-blinded, randomized controlled trial.

BACKGROUND: Topical anesthesia is a crucial step in awake endotracheal intubation for providing favorable intubation conditions. The standard of care technique for awake intubation at our institution, which consists of oropharyngeal tetracaine spray, can result in inadequate mucosal anesthesia. Therefore, we sought to compare the effectiveness of dyclonine hydrochloride mucilage to the standard of care tetracaine in achieving anesthesia of the upper airways for awake endotracheal intubation. METHODS: This is a randomized, assessor-blinded, prospective study. From Jun. 1st, 2019 to Aug. 1st, 2019, patients scheduled for either endoscopic submucosal dissection or peroral endoscopic myotomy were enrolled and randomly allocated into two groups after obtaining written informed consent: patients allocated to novel awake intubation care (Group N-AIC) received a single administration of oral dyclonine hydrochloride mucilage, whereas patients allocated to standard awake intubation care (Group S-AIC) received three oropharyngeal tetracaine sprays before transcricoid tetracaine injection before awake intubation. Mean arterial pressure (MAP), which was the primary outcome of this study, as well as heart rate (HR) were recorded throughout the procedure and compared between the two groups. Feeling of numbness, nausea, and intubation conditions after topical anesthesia were also assessed. RESULTS: Sixty patients were enrolled and completed the study. Baseline MAP and HR were similar between the two groups. However, hemodynamic responses to intubation and gastrointestinal endoscopy, especially MAP, were significantly less elevated in Group N-AIC. The degree of numbness of the oropharyngeal mucosa after topical anesthesia did not differ between the two groups, neither did the feeling of nausea during laryngoscopy. The amount of pharyngeal secretions before intubation was less in Group N-AIC. Total intubation time was significantly shorter in Group N-AIC when compared to Group S-AIC (18.4 ± 2.86 vs. 22.3 ± 6.47, P < 0.05). Extubation bucking was significantly less frequent in Group N-AIC (13.3% vs. 76.7%). Patients received in Group N-AIC had a lower rate of post-extubation sore throat compared to Group S-AIC (6.7% vs. 43.3%). No adverse side effects attributable to either tetracaine or dyclonine were observed in this study. CONCLUSIONS: In awake endotracheal intubation, novel care using oral dyclonine hydrochloride mucilage can provide more favorable mucosal anesthesia and better intubation conditions compared to standard of care practice using oropharyngeal tetracaine spray. TRIAL REGISTRATION: ChiCTR1900023151 . Date of registration: May 14th, 2019.

Xanthohumol inhibits PRRSV proliferation and alleviates oxidative stress induced by PRRSV via the Nrf2-HMOX1 axis.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent and endemic swine pathogen that causes significant economic losses in the global swine industry. Commercial vaccines provide limited protection against this virus, and no highly effective therapeutic drugs are yet available. In this study, we first screened a library of 386 natural products and found that xanthohumol (Xn), a prenylated flavonoid found in hops, displayed high anti-PRRSV activity by inhibiting PRRSV adsorption onto and internalization into cells. Transcriptome sequencing revealed that Xn treatment stimulates genes associated with the antioxidant response in the nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. Xn causes increased expression of Nrf2, HMOX1, GCLC, GCLM, and NQO1 in Marc-145 cells. The action of Xn against PRRSV proliferation depends on Nrf2 in Marc-145 cells and porcine alveolar macrophages (PAMs). This finding suggests that Xn significantly inhibits PRRSV proliferation and decreases viral-induced oxidative stress by activating the Nrf2-HMOX1 pathway. This information should be helpful for developing a novel prophylactic and therapeutic strategy against PRRSV infection.

Pharmacokinetic and bioequivalence study of sugar-coated and film-coated eperisone tablets in healthy subjects: A randomized, open-label, three-way, reference-replicated crossover study
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OBJECTIVE: Eperisone hydrochloride is used in the treatment of musculoskeletal disorders as a muscle relaxant via blocking of calcium channels. In this study, we aimed to investigate the within-subject variability (CVwR) of reference eperisone formulation for highly-variable drugs and to perform bioequivalence study of two oral formulations (sugar- and film-coated tablets) of eperisone hydrochloride 50 mg in healthy subjects by reference-replicated crossover study. MATERIALS AND METHODS: 36 healthy Korean male subjects were recruited, and 33 subjects completed the study. A randomized, single-dose, open-label, three-way, three-sequence, reference formulation-replicated, crossover bioequivalence study was conducted to determine the bioequivalence of eperisone. Blood samples were collected before dosing and at 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after dosing. The plasma concentration of eperisone was determined using liquid chromatography-tandem mass spectrometry. RESULTS: The CVwR of eperisone reference product was 33.17% for AUCt and 50.21% for Cmax. The acceptance limit for Cmax was scaled to 0.6984 - 1.4319 according to CVwR. The 90% confidence intervals for the test/reference geometric mean ratio were 0.8275 - 1.1692 for AUCt and 0.7587 - 1.1652 for Cmax, which were within the accepted bioequivalence limits. Single oral doses of eperisone hydrochloride 50 mg were generally well tolerated in healthy adult subjects in this study. CONCLUSION: The newly developed film-coated tablet can be interchanged with the original sugar-coated tablet of eperisone. In addition, the reference scaling methods are more effective and economical than the classical method for assessing BE of HVDs.
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Xanthohumol inhibits angiogenesis by suppressing nuclear factor-κB activation in pancreatic cancer.

Xantohumol, a prenylated chalcone from hops (Humulus lupulus L.), has been shown to inhibit proliferation in some cancers. However, little is known regarding the effects of xanthohumol in pancreatic cancer. We have previously reported that activation of the transcription factor nuclear factor-κB (NF-κB) plays a key role in angiogenesis in pancreatic cancer. In this study, we investigated whether xanthohumol inhibited angiogenesis by blocking NF-κB activation in pancreatic cancer in vitro and in vivo. We initially confirmed that xanthohumol significantly inhibited proliferation and NF-κB activation in pancreatic cancer cell lines. Next, we demonstrated that xanthohumol significantly suppressed the expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) at both the mRNA and protein levels in pancreatic cancer cell lines. We also found that coculture with BxPC-3 cells significantly enhanced tube formation in human umbilical vein endothelial cells, and treatment with xanthohumol significantly blocked this effect. In vivo, the volume of BxPC-3 subcutaneous xenograft tumors was significantly reduced in mice treated with weekly intraperitoneal injections of xanthohumol. Immunohistochemistry revealed that xanthohumol inhibited Ki-67 expression, CD31-positive microvessel density, NF-κB p65 expression, and VEGF and IL-8 levels. Taken together, these results showed, for the first time, that xanthohumol inhibited angiogenesis by suppressing NF-κB activity in pancreatic cancer. Accordingly, xanthohumol may represent a novel therapeutic agent for the management of pancreatic cancer.

Sub-optimal Application of a High SPF Sunscreen Prevents Epidermal DNA Damage in Vivo.

The cyclobutane pyrimidine dimer (CPD) is a potentially mutagenic DNA photolesion that is the basis of most skin cancers. There are no data on DNA protection by sunscreens under typical conditions of use. The study aim was to determine such protection, in phototypes I/II, with representative sunscreen-user application. A very high SPF formulation was applied at 0.75, 1.3 and 2.0 mg/cm2. Unprotected control skin was exposed to 4 standard erythema doses (SED) of solar simulated UVR, and sunscreen-treated sites to 30 SED. Holiday behaviour was also simulated by UVR exposure for 5 consecutive days. Control skin received 1 SED daily, and sunscreen-treated sites received 15 (all 3 application thicknesses) or 30 (2.0 mg/cm2) SED daily. CPD were assessed by quantitative HPLC-tandem mass spectrometry (HPLC-MS/MS) and semi-quantitative immunostaining. In comparison with unprotected control sites, sunscreen significantly (p ≤ 0.001-0.05) reduced DNA damage at 1.3 and 2.0 mg/cm2 in all cases. However, reduction with typical sunscreen use (0.75 mg/cm2) was non-significant, with the exception of HPLC-MS/MS data for the 5-day study (p <0.001). Overall, these results support sunscreen use as a strategy to reduce skin cancer, and demonstrate that public health messages must stress better sunscreen application to get maximal benefit.

[When sunscreens do not help: allergic contact dermatitis to UV filters]. / Wenn Sonnenschutzprodukte nicht mehr helfen: Allergisches Kontaktekzem auf UV-Filter.

Ultraviolet (UV) filters may cause allergic and more frequently photoallergic contact dermatitis. Therefore, a photopach test should always be performed in case of a suspected contact sensitivity to UV filters. We report a case of a 65-year-old woman with a recurrent erythema of the face and décolleté after sun exposure despite application of a sunscreen. The (photo)patch test revealed a contact sensitivity to the UV filter butyl-methoxybenzoylmethane. Treatment with a topical glucocorticoid and avoidance of the particular UV filter led to a rapid improvement.

Oral dyclonine hydrochloride mucilage versus tetracaine spray in electronic flexible laryngoscopy: A prospective, randomized controlled trial.

BACKGROUND: Topical anesthesia is important for electronic flexible laryngoscopy (EFL) utilization. We hypothesized that oral dyclonine hydrochloride mucilage (ODHM) is superior to tetracaine spray (TS) in patients undergoing EFL examination. METHODS: This study included 932 patients randomized into either an ODHM or TS group, in which patients received either a single utilization of ODHM or TS administered via spray in three intervals. A 4.9 mm diameter flexible PENTAX-VNL-1570STK insertion tube placed into a Naso-Pharyngo-Laryngoscope (PENTAX Medical, Japan) was used in the procedure. Visual analogue scale (VAS) (0-10) was used to evaluate patient tolerance and procedure success by the operator, independently. Procedure time was also recorded. RESULTS: Both patients' and doctors' VAS scores were significantly higher in the ODHM group compared to the TS group. When subgroup analysis was made according to the procedure length (100 s), there was no significant difference in VAS between ODHM and TS groups in the short time procedure (≤100 s), while VAS in the ODHM group was higher compared to the TS in the long time procedure (>100 s), as assessed by both patients and doctors. CONCLUSION: A single use of ODHM seems to be superior to three doses of TS in patients undergoing EFL, specifically in procedures longer than 100seconds.

Is there any difference in patterns of use and psychiatric symptom status between injectors and non-injectors of mephedrone?

OBJECTIVE: In recent years, increasing intravenous mephedrone use was reported in several countries. The aim of this study was to describe the characteristics of such a form of mephedrone use, while identifying the differences between injectors and non-injectors in patterns of mephedrone use and psychiatric symptom status. METHODS: One hundred and forty-five mephedrone users were surveyed on patterns of mephedrone use using a structured questionnaire as well as the Brief Symptom Inventory. RESULTS: Majority of users received mephedrone from acquaintances and used it in discos/parties settings regarding both first and current mephedrone use. Intranasal use was the most typical route of administration (84.4%). Injectors (11%) used the drug more frequently and in higher dosages. This group included a greater proportion of opiate users (37.5%) and showed more diffuse psychiatric symptoms. Regarding the predictors of being an injector, heroin use showed the highest odds ratio. CONCLUSIONS: Intravenous mephedrone use is associated with a higher risk of harmful drug use, elevated psychiatric symptom profile and increased possibility of mephedrone being considered as an addictive substance. These findings might be important in efficient treatment planning.

[Cognitive dysfunctions caused by excessive exposure to manganese compounds. Cognitive disturbances in intravenous users of ephedrone (methcathinone) with manganese compounds]. / Zaburzenia funkcji poznawczych spowodowane nadmierna ekspozycja na zwiazki manganu. Zaburzenia funkcji poznawczych u dozylnych uzytkowników preparatów efedronu (metkatynonu).

Intravenous injection of self-produced ephedrone (metcathinone) using potassium permanganate as an oxidant can lead to severe, fixed encephalopathy. This risk applies mainly to young individuals experimenting with "home-made" drugs and results in an irreversible aggravation of overall functioning. Besides multiple neurological symptoms and movement disorders, affected individuals also experience cognitive dysfunction. No systematic research has been conducted in this field. Single case reports and small group descriptions show that assessment with screening tools such as the Mini-Mental State Examination (MMSE) is ineffective. Neuropsychological assessment conducted with other tests indicates significant dysarthric speech disorders, psychomotor function impairment, attentional disorders of varying intensity as well as dysfunctions of verbal and visual working memory processes. Some studies of this group of subjects also indicate working memory and executive function disorders. These dysfunctions seem to be permanent and do not recede following manganese use discontinuation and an improvement of the neuroradiological picture in MRI assessment. A standard test battery should be developed enabling the assessment of both cognitive and neurological dysfunctions that otherwise render some tests impossible to administer.

Effect of xanthohumol and 8-prenylnaringenin on MCF-7 breast cancer cells oxidative stress and mitochondrial complexes expression.

Xanthohumol (XN) and 8-prenylnaringenin (8PN) are hop (Humulus lupulus L.) polyphenols studied for their chemopreventive effects on certain cancer types. The breast cancer line MCF-7 was treated with doses ranging from 0.001 to 20 µM of XN or 8PN in order to assess the effects on cell viability and oxidative stress. Hoechst 33342 was used to measure cell viability and reactive oxygen species (ROS) production was determined by 2',7'-dichlorofluorescein diacetate. Catalase, superoxide dismutase, and glutathione reductase enzymatic activities were determined and protein expression of sirtuin1, sirtuin3, and oxidative phosphorylation system (OXPHOS) were done by Western blot. Treatments XN 0.01, 8PN 0.01, and 8PN 1 µM led to a decrease in ROS production along with an increase of OXPHOS and sirtuin expression; in contrast, XN 5 µM gave rise to an increase of ROS production accompanied by a decrease in OXPHOS and sirtuin expression. These results suggest that XN in low dose (0.01 µM) and 8PN at all assayed doses (0.001-20 µM) presumably improve mitochondrial function, whereas a high dose of XN (5 µM) worsens the functionality of this organelle.

Xanthohumol impairs human prostate cancer cell growth and invasion and diminishes the incidence and progression of advanced tumors in TRAMP mice.

Despite recent advances in understanding the biological basis of prostate cancer, management of the disease, especially in the phase resistant to androgen ablation, remains a significant challenge. The long latency and high incidence of prostate carcinogenesis provides the opportunity to intervene with chemoprevention to prevent or eradicate prostate malignancies. In this study, we have used human hormone-resistant prostate cancer cells, DU145 and PC3, as an in vitro model to assess the efficacy of xanthohumol (XN) against cell growth, motility and invasion. We observed that treatment of prostate cancer cells with low micromolar doses of XN inhibits proliferation and modulates focal adhesion kinase (FAK) and AKT phosphorylation leading to reduced cell migration and invasion. Oxidative stress by increased production of reactive oxygen species (ROS) was associated with these effects. Transgenic adenocarcinoma of the mouse prostate (TRAMP) transgenic mice were used as an in vivo model of prostate adenocarcinoma. Oral gavage of XN, three times per week, beginning at 4 wks of age, induced a decrease in the average weight of the urogenital (UG) tract, delayed advanced tumor progression and inhibited the growth of poorly differentiated prostate carcinoma. The ability of XN to inhibit prostate cancer in vitro and in vivo suggests that XN may be a novel agent for the management of prostate cancer.

Xanthohumol inhibits growth and vascularization of developing endometriotic lesions.

BACKGROUND: Xanthohumol is a prenylated flavonoid isolated from hops, which is known to act as a pleiotropic cancer chemopreventive agent owing to its anti-proliferative, anti-inflammatory and anti-angiogenic properties. In the present study, we analyzed, for the first time, whether this dietary compound may also be used for the treatment of endometriosis. METHODS: Peritoneal and mesenteric endometriotic lesions were surgically induced in BALB/c mice by uterine tissue transplantation into the abdominal cavity. The animals were treated daily with 100 µM xanthohumol (n= 8) or vehicle (control, n= 8) via the drinking water, starting 3 days before tissue transplantations. Lesion growth, cyst formation and vascularization were subsequently analyzed by means of high-resolution ultrasound imaging (at Day 0 and then once per week for 28 days), caliper measurements, western blotting, histology and immunohistochemistry over 4 weeks. RESULTS: In the treatment and control groups, uterine grafts developed typical endometriotic lesions with cyst-like dilated glands surrounded by a vascularized endometrial stroma. However, xanthohumol efficiently decreased the size of these lesions at Day 28, independent of their localization within the peritoneal cavity, compared with control (peritoneal: P =0.041; mesenteric: P =0.038). This was associated with a reduced level of phosphoinositide 3-kinase protein. Moreover, vascularization of xanthohumol-treated lesions was suppressed, as indicated by a significantly lower microvessel density at Day 28 when compared with vehicle-treated controls (peritoneal: P =0.026; mesenteric: P =0.004). Additional analyses revealed that treatment with xanthohumol did not affect the histomorphology, proliferation and vascularization of the uterine horns and ovaries. CONCLUSIONS: Taken together, these experimental findings suggest that xanthohumol inhibits the development of endometriotic lesions in mice without inducing serious side effects in the reproductive organs. Thus, xanthohumol represents a promising dietary phytochemical that, after further testing, may be considered for the use in the selective treatment of endometriotic lesions.

Dietary prenylated flavonoid xanthohumol alleviates oxidative damage and accelerates diabetic wound healing via Nrf2 activation.

Diabetic skin ulcer is one of the most common complications in patients suffering diabetes mellitus. Xanthohumol (XN), a hop-derived prenylated dietary flavonoid, has multiple health beneficial bioactivities. In the present study, we reported XN alleviates oxidative damage and accelerates diabetic wound healing via Nrf2 activation. In vitro, XN attenuated hydrogen peroxide (H2O2)-induced cytotoxicity, ROS production, cell apoptosis, as well as high glucose-induced cell damage. Mechanistic studies further demonstrated that XN could stabilize nuclear factor erythroid 2-related factor 2 (Nrf2) and promote its nuclear translocation, which was associated with AMPKα activation and covalent modification of Keap1 by XN. In vivo, XN increased Nrf2 expression and accelerated diabetic wound healing. Our study revealed a novel function of XN in diabetic wound healing as well as the underlying molecular mechanisms, suggesting XN is a promising lead compound and a potential food and/or drug candidate for the treatment of diabetic skin ulcers.

Preventive but Not Therapeutic Topical Application of Local Anesthetics Can Inhibit Experimental Epidermolysis Bullosa Acquisita in Mice.

Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disorder characterized and caused by autoantibodies against type VII collagen (COL7). Although it has been noticed that EBA in both patients and mice is associated with an increased scratching, it is not clear whether and how the scratching contributes to disease manifestation. Hence, we here aimed to validate this clinical observation and also to investigate the potential contribution of increased scratching in EBA pathogenesis in mice. Longitudinal assessment of scratching behavior revealed an increased frequency of scratching as early as 12 hours after injection of anti-COL7 IgG into the skin of mice. Subsequently, scratching events became even more frequent in mice. In contrast, mice injected with a control antibody showed an unaltered scratching behavior throughout the observation period. Based on these observations, we hypothesized that mechanical irritation may promote the induction of inflammation in experimental EBA. To challenge this assumption, the local anesthetic dyclonine hydrochloride was topically applied before injection of anti-COL7 IgG. Dyclonine hydrochloride reduced the scratching events and impaired clinical disease manifestation. In therapeutic experimental settings, i.e. administration of the local anesthetic 24 hours after injection of anti-COL7 IgG, dyclonine hydrochloride only inhibited the scratching behavior, but had no significant effect on clinical disease development. In addition, eosinophils were detected in the skin before the injection of anti-COL7 IgG and significantly increased 48 hours after the antibody injection. Collectively, our results suggest that scratching behavior contributes to the initiation phase of disease manifestation in experimental EBA.

Behavioral Effects of 4-CMC and 4-MeO-PVP in DBA/2J Mice After Acute and Intermittent Administration and Following Withdrawal from Intermittent 14-Day Treatment.

Synthetic cathinones appeared on the market in the 2000s as new psychoactive substances and gained significant prevalence among drug abusers. Cathinones produce psychostimulant and empathogenic effects by enhancing dopaminergic, noradrenergic, and serotoninergic neurotransmission in the brain, and those which potently and selectively enhance dopaminergic transmission are considered to have higher abuse potential. The present study examines the behavioral effects related to psychostimulant properties, abuse potential, and addiction in DBA/2J mice of two cathinones with different profile of action on monoamine system, 4-chloromethcathinone (4-CMC), and 4-methoxy-pyrrolidinopentiophenone (4-MeO-PVP). 4-CMC and 4-MeO-PVP increase spontaneous locomotor activity after acute treatment and produce behavioral sensitization after 7-day intermittent treatment, which is a common feature of drugs of abuse. 4-MeO-PVP, but not 4-CMC, produces conditioned place preference after 4 days, indicating its rewarding properties. Finally, the ability of 4-CMC and 4-MeO-PVP to induce withdrawal symptoms after discontinuation from 14-day treatment was assessed using a battery of tests for behavioral markers of depression in mice: a tail suspension test, a forced swim test, measuring despair, and a sucrose preference test, measuring anhedonia. None of the three tests revealed increased depressive symptoms. Moreover, neither spontaneous locomotor activity nor motor performance on a rotarod was impaired after 14-day treatment with the tested compounds. These results indicate that 14-day treatment of mice with 4-CMC or 4-MeO-PVP does not induce significant withdrawal symptoms after cessation, nor significant impairment of dopaminergic circuitry resulting in motor impairment. The current study shows that 4-CMC and 4-MeO-PVP produce abuse-related behavioral changes in mice, which are more pronounced after more dopamine-selective 4-MeO-PVP.