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Pharmacology of novel synthetic stimulants structurally related to the "bath salts" constituent 3,4-methylenedioxypyrovalerone (MDPV).
Neuropharmacology. 2014 Dec; 87:206-13.N

Abstract

There has been a dramatic rise in the abuse of synthetic cathinones known as "bath salts," including 3,4-methylenedioxypyrovalerone (MDPV), an analog linked to many adverse events. MDPV differs from other synthetic cathinones because it contains a pyrrolidine ring which gives the drug potent actions as an uptake blocker at dopamine and norepinephrine transporters. While MDPV is now illegal, a wave of "second generation" pyrrolidinophenones has appeared on the market, with α-pyrrolidinovalerophenone (α-PVP) being most popular. Here, we sought to compare the in vitro and in vivo pharmacological effects of MDPV and its congeners: α-PVP, α-pyrrolidinobutiophenone (α-PBP), and α-pyrrolidinopropiophenone (α-PPP). We examined effects of test drugs in transporter uptake and release assays using rat brain synaptosomes, then assessed behavioral stimulant effects in mice. We found that α-PVP is a potent uptake blocker at dopamine and norepinephrine transporters, similar to MDPV. α-PBP and α-PPP are also catecholamine transporter blockers but display reduced potency. All of the test drugs are locomotor stimulants, and the rank order of in vivo potency parallels dopamine transporter activity, with MDPV > α-PVP > α-PBP > α-PPP. Motor activation produced by all drugs is reversed by the dopamine receptor antagonist SCH23390. Furthermore, results of a functional observational battery show that all test drugs produce typical stimulant effects at lower doses and some drugs produce bizarre behaviors at higher doses. Taken together, our findings represent the first evidence that second generation analogs of MDPV are catecholamine-selective uptake blockers which may pose risk for addiction and adverse effects in human users. This article is part of the Special Issue entitled 'CNS Stimulants'.

Authors+Show Affiliations

RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA. Electronic address: jmarusich@rti.org.RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA.RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA.RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709, USA.Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24594476

Citation

Marusich, Julie A., et al. "Pharmacology of Novel Synthetic Stimulants Structurally Related to the "bath Salts" Constituent 3,4-methylenedioxypyrovalerone (MDPV)." Neuropharmacology, vol. 87, 2014, pp. 206-13.
Marusich JA, Antonazzo KR, Wiley JL, et al. Pharmacology of novel synthetic stimulants structurally related to the "bath salts" constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology. 2014;87:206-13.
Marusich, J. A., Antonazzo, K. R., Wiley, J. L., Blough, B. E., Partilla, J. S., & Baumann, M. H. (2014). Pharmacology of novel synthetic stimulants structurally related to the "bath salts" constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology, 87, 206-13. https://doi.org/10.1016/j.neuropharm.2014.02.016
Marusich JA, et al. Pharmacology of Novel Synthetic Stimulants Structurally Related to the "bath Salts" Constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology. 2014;87:206-13. PubMed PMID: 24594476.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacology of novel synthetic stimulants structurally related to the "bath salts" constituent 3,4-methylenedioxypyrovalerone (MDPV). AU - Marusich,Julie A, AU - Antonazzo,Kateland R, AU - Wiley,Jenny L, AU - Blough,Bruce E, AU - Partilla,John S, AU - Baumann,Michael H, Y1 - 2014/03/02/ PY - 2013/11/29/received PY - 2014/02/05/revised PY - 2014/02/20/accepted PY - 2014/3/6/entrez PY - 2014/3/7/pubmed PY - 2015/8/5/medline KW - 3,4-Methylenedioxypyrovalerone KW - Functional observational battery KW - Locomotor activity KW - Monoamine transporter KW - Synthetic cathinones KW - α-PVP SP - 206 EP - 13 JF - Neuropharmacology JO - Neuropharmacology VL - 87 N2 - There has been a dramatic rise in the abuse of synthetic cathinones known as "bath salts," including 3,4-methylenedioxypyrovalerone (MDPV), an analog linked to many adverse events. MDPV differs from other synthetic cathinones because it contains a pyrrolidine ring which gives the drug potent actions as an uptake blocker at dopamine and norepinephrine transporters. While MDPV is now illegal, a wave of "second generation" pyrrolidinophenones has appeared on the market, with α-pyrrolidinovalerophenone (α-PVP) being most popular. Here, we sought to compare the in vitro and in vivo pharmacological effects of MDPV and its congeners: α-PVP, α-pyrrolidinobutiophenone (α-PBP), and α-pyrrolidinopropiophenone (α-PPP). We examined effects of test drugs in transporter uptake and release assays using rat brain synaptosomes, then assessed behavioral stimulant effects in mice. We found that α-PVP is a potent uptake blocker at dopamine and norepinephrine transporters, similar to MDPV. α-PBP and α-PPP are also catecholamine transporter blockers but display reduced potency. All of the test drugs are locomotor stimulants, and the rank order of in vivo potency parallels dopamine transporter activity, with MDPV > α-PVP > α-PBP > α-PPP. Motor activation produced by all drugs is reversed by the dopamine receptor antagonist SCH23390. Furthermore, results of a functional observational battery show that all test drugs produce typical stimulant effects at lower doses and some drugs produce bizarre behaviors at higher doses. Taken together, our findings represent the first evidence that second generation analogs of MDPV are catecholamine-selective uptake blockers which may pose risk for addiction and adverse effects in human users. This article is part of the Special Issue entitled 'CNS Stimulants'. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/24594476/Pharmacology_of_novel_synthetic_stimulants_structurally_related_to_the_"bath_salts"_constituent_34_methylenedioxypyrovalerone__MDPV__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(14)00080-X DB - PRIME DP - Unbound Medicine ER -