Behavioral evidence for the abuse potential of the novel synthetic cathinone alpha-pyrrolidinopentiothiophenone (PVT) in rodents

Cheong, Jae Hoon; Choi, Mee Jung; Jang, Choon‐Gon; Lee, Yong Sup; Lee, Sooyeun; Kim, Hee Jin; Seo, Joung‐Wook; Yoon, Seong Shoon

doi:10.1007/s00213-017-4526-8

Cited by 32 publications

(49 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4-MePPP did not fully substitute for cocaine in rats (Gatch et al, 2015a), nor did mephedrone (4-methylmethcathinone) fully substitute in rhesus monkeys (Smith et al, 2016), despite fully substituting for cocaine in rats (Gatch et al, 2013). It should be noted that α-PVT has been reported to produce full substitution in both cocaine- and methamphetamine-trained rats (Cheong et al, 2017), although that study used a lower training dose of cocaine (5.6 mg/kg). There is still a possibility that mephedrone does not have robust cocaine-like discriminative stimulus effects as rats trained to discriminate mephedrone from saline did not fully generalize to cocaine (Varner et al 2013).…”

Section: Discussionmentioning

confidence: 95%

Locomotor activity and discriminative stimulus effects of a novel series of synthetic cathinone analogs in mice and rats

2017

View full text Add to dashboard Cite

Rationale Recent years have seen an increase in the recreational use of novel, synthetic psychoactive substances. There are little or no data on the abuse liability of many of the newer compounds. Objectives The current study investigated the discriminative stimulus and locomotor effects of a series of synthetic analogues of cathinone: alpha-PPP, alpha-PHP, alpha-PVT, 3,4-methylenedioxy-PBP (MDPBP), and ethylone. Methods Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine or methamphetamine from vehicle. Results Each of the compounds produced an inverted-U dose-effect on locomotor activity. Maximal effects were similar among the test compounds, but potencies varied with relative potencies of MDPBP>α-PPP=α-PHP>ethylone>α-PVT. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine. α-PPP, α-PHP, and ethylone fully substituted for cocaine. α-PVT produced a maximum of 50% cocaine-appropriate responding and MDPBP produced an inverted U-shaped dose-effect curve with maximum effects of 67%. Conclusions These data provide initial evidence that these structurally-similar, emerging novel psychoactive substances demonstrate potential for abuse and may be utilized for their stimulant-like effects, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of the classical psychostimulants cocaine and/or methamphetamine.

show abstract

Section: Discussionmentioning

confidence: 95%

Locomotor activity and discriminative stimulus effects of a novel series of synthetic cathinone analogs in mice and rats

2017

View full text Add to dashboard Cite

show abstract

“…16 Recent research on the pyrovalerone analogue α-pyrrolidinopentiothiophenone (α-PVT) suggests it has reinforcing and rewarding effects similar to those of both methylamphetamine and cocaine. 17 It has been suggested that the reinforcing properties of cathinone stimulants are positively correlated with their selectivity for the dopamine (DAT) relative to SERT. 15,[18][19][20] What is already known about this subject • NPSfinder ® has identified some 41 cathinone molecules not known to either the UNODC or EMCDDA.…”

Section: Clinical Neuropharmacological Issuesmentioning

confidence: 99%

“…MDPV and α‐PVP are both considered to be cocaine‐like, whilst being more effective reinforcers . Recent research on the pyrovalerone analogue α‐pyrrolidinopentiothiophenone (α‐PVT) suggests it has reinforcing and rewarding effects similar to those of both methylamphetamine and cocaine …”

Section: Introductionmentioning

confidence: 99%

The clinical challenges of synthetic cathinones

Schifano

Napoletano

Arillotta

et al. 2020

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims Within the new psychoactive substances (NPS) scenario, several hundred different molecules, mostly including synthetic cannabinoids and cathinones, have been identified so far. The aims of the paper were to: (i) identify the number of synthetic cathinones mentioned in a range of psychonaut, NPS‐related, online sources; and (ii) describe the associated acute/long term clinical scenario and the related treatment/management plan. Methods After about 18 months of operation and exclusion of false positives/duplicates, some 4204 unique NPS molecules were included in the NPSfinder® crawling/navigating software database. Most popular NPS included: 1265 psychedelic phenethylamines (30.1%; confidence interval [CI] 95%: 28.7–31.5%); 1253 synthetic cannabinoids (29.8%; CI 95%: 28.4–31.2%); 429 synthetic opioids (10.2%; CI 95%: 9.3–10.2%); and 171 synthetic cathinones (4.1%; CI 95% 3.5–4.7%). Conversely, the United Nations Office on Drugs and Crime and the European Monitoring Centre for Drugs and Drug Addiction databases respectively included 169 and 140 cathinones. Overall, the 3 databases reported some 222 synthetic cathinones, and 41 were uniquely identified by the NPSfinder®. Results In terms of clinical scenarios, synthetic cathinone ingestion is initially associated with stimulant effects; however, psychopathological disturbances, violence, suicidal behaviour, hyperthermia, coma and death have also been described. Conclusion The proportion of cathinones commented on by psychonaut fora appeared to be relatively small, and similar to those reported by both the United Nations Office on Drugs and Crime and European Monitoring Centre for Drugs and Drug Addiction. This may be associated with a recent significant decline in both cathinone‐related consumption and acute medical presentation. Due to their complex behavioural and medical toxicity issues, healthcare professionals should be, however, be educated to recognise the signs and symptoms of NPS, including synthetic cathinone, ingestion.

show abstract

“…Significance place conditioning was additionally observed for the phenyl/thiophene substitute of α -PVP, α- pyrrolidinopentiothiophenone ( α -PVT). 67…”

Section: Behavioral Effects Of Synthetic Cathinones Determined From Cmentioning

confidence: 99%

DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants

Simmons

Leyrer‐Jackson

Oliver

et al. 2018

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Cathinone is a plant alkaloid found in khat leaves of perennial shrubs grown in East Africa. Similar to cocaine, cathinone elicits psychostimulant effects which are in part attributed to its amphetamine-like structure. Around 2010, home laboratories began altering the parent structure of cathinone to synthesize derivatives with mechanisms of action, potencies, and pharmacokinetics permitting high abuse potential and toxicity. These "synthetic cathinones" include 4-methylmethcathinone (mephedrone), 3,4-methylenedioxypyrovalerone (MDPV), and the empathogenic agent 3,4-methylenedioxymethcathinone (methylone) which collectively gained international popularity following aggressive online marketing as well as availability in various retail outlets. Case reports made clear the health risks associated with these agents and, in 2012, the Drug Enforcement Agency of the United States placed a series of synthetic cathinones on Schedule I under emergency order. Mechanistically, cathinone and synthetic derivatives work by augmenting monoamine transmission through release facilitation and/or presynaptic transport inhibition. Animal studies confirm the rewarding and reinforcing properties of synthetic cathinones by utilizing self-administration, place conditioning, and intracranial self-stimulation assays and additionally show persistent neuropathological features which demonstrate a clear need to better understand this class of drugs. This Review will thus detail (i) historical context of cathinone use and the rise of "dark" synthetic derivatives, (ii) structural features and mechanisms of synthetic cathinones, (iii) behavioral effects observed clinically and in animals under controlled laboratory conditions, and (iv) neurotransmitters and circuits that may be targeted to manage synthetic cathinone abuse in humans.

show abstract

Behavioral evidence for the abuse potential of the novel synthetic cathinone alpha-pyrrolidinopentiothiophenone (PVT) in rodents

Cited by 32 publications

References 28 publications

Locomotor activity and discriminative stimulus effects of a novel series of synthetic cathinone analogs in mice and rats

Locomotor activity and discriminative stimulus effects of a novel series of synthetic cathinone analogs in mice and rats

The clinical challenges of synthetic cathinones

DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants

Contact Info

Product

Resources

About