Impure but not inactive: Behavioral pharmacology of dibenzylpiperazine, a common by-product of benzylpiperazine synthesis

Research output: Contribution to journalArticle

Abstract

Background: Substituted piperazines comprise a substantial proportion of the novel psychoactive substance market. Among the most widely abused piperazine compounds are meta-chlorophenylpiperazine (mCPP), tri-fluoromethylphenylpiperazine (TFMPP), and, especially, benzylpiperazine (BZP), which are commonly incorporated, either alone or in combination, in illicit “party pills” or “ecstasy” formulations. Illicit synthesis of BZP often results in production of an impure by-product dibenzylpiperazine (DBZP), which frequently appears alongside BZP in these formulations; however, despite its ubiquity, little information exists regarding the abuse liability of DBZP. Aims: The current study aimed to evaluate the abuse-related behavioral pharmacology of DBZP. Methods: DBZP, mCPP, and TFMPP were tested in parallel in mice in locomotor activity and conditioned place preference assays, and in a drug discrimination assay with rats trained to discriminate either methamphetamine, cocaine, (±)-3,4-methylenedioxymethamphetamine (MDMA), or -2,5-dimethoxy-4-methylamphetamine(DOM). Results: Each of the compounds tested produced dose-dependent decreases in locomotor activity. DBZP substituted fully for methamphetamine, produced subthreshold drug-appropriate responding for cocaine and MDMA, and failed to substitute for DOM. Conversely, TFMPP and mCPP only produced subthreshold drug-appropriate responding for methamphetamine and MDMA, respectively, and both compounds failed to substitute for cocaine or DOM. None of the compounds tested produced a place preference. DBZP produced convulsions in rats at the highest dose tested. Conclusions: These data indicate that DBZP is more similar to BZP, albeit with lower potency and efficacy, than its serotonergic piperazine counterparts, and is a behaviorally-active compound with some abuse liability and potential for adverse health effects.

Original languageEnglish
Pages (from-to)802-810
Number of pages9
JournalJournal of Psychopharmacology
Volume32
Issue number7
DOIs
StatePublished - 1 Jul 2018

Fingerprint

2,5-Dimethoxy-4-Methylamphetamine
N-Methyl-3,4-methylenedioxyamphetamine
Methamphetamine
Cocaine
Pharmacology
Locomotion
Piperazines
Pharmaceutical Preparations
Seizures
Health
1-(3-chlorophenyl)piperazine
piperazine

Keywords

  • Abuse liability
  • DBZP
  • conditioned place preference
  • drug discrimination

Cite this

@article{f9a7abf72523433a89fd80a58014489e,
title = "Impure but not inactive: Behavioral pharmacology of dibenzylpiperazine, a common by-product of benzylpiperazine synthesis",
abstract = "Background: Substituted piperazines comprise a substantial proportion of the novel psychoactive substance market. Among the most widely abused piperazine compounds are meta-chlorophenylpiperazine (mCPP), tri-fluoromethylphenylpiperazine (TFMPP), and, especially, benzylpiperazine (BZP), which are commonly incorporated, either alone or in combination, in illicit “party pills” or “ecstasy” formulations. Illicit synthesis of BZP often results in production of an impure by-product dibenzylpiperazine (DBZP), which frequently appears alongside BZP in these formulations; however, despite its ubiquity, little information exists regarding the abuse liability of DBZP. Aims: The current study aimed to evaluate the abuse-related behavioral pharmacology of DBZP. Methods: DBZP, mCPP, and TFMPP were tested in parallel in mice in locomotor activity and conditioned place preference assays, and in a drug discrimination assay with rats trained to discriminate either methamphetamine, cocaine, (±)-3,4-methylenedioxymethamphetamine (MDMA), or -2,5-dimethoxy-4-methylamphetamine(DOM). Results: Each of the compounds tested produced dose-dependent decreases in locomotor activity. DBZP substituted fully for methamphetamine, produced subthreshold drug-appropriate responding for cocaine and MDMA, and failed to substitute for DOM. Conversely, TFMPP and mCPP only produced subthreshold drug-appropriate responding for methamphetamine and MDMA, respectively, and both compounds failed to substitute for cocaine or DOM. None of the compounds tested produced a place preference. DBZP produced convulsions in rats at the highest dose tested. Conclusions: These data indicate that DBZP is more similar to BZP, albeit with lower potency and efficacy, than its serotonergic piperazine counterparts, and is a behaviorally-active compound with some abuse liability and potential for adverse health effects.",
keywords = "Abuse liability, DBZP, conditioned place preference, drug discrimination",
author = "Dolan, {Sean B.} and Shetty, {Ritu A.} and Forster, {Michael J.} and Gatch, {Michael B.}",
year = "2018",
month = "7",
day = "1",
doi = "10.1177/0269881118780613",
language = "English",
volume = "32",
pages = "802--810",
journal = "Journal of Psychopharmacology",
issn = "0269-8811",
publisher = "SAGE Publications Ltd",
number = "7",

}

TY - JOUR

T1 - Impure but not inactive

T2 - Behavioral pharmacology of dibenzylpiperazine, a common by-product of benzylpiperazine synthesis

AU - Dolan, Sean B.

AU - Shetty, Ritu A.

AU - Forster, Michael J.

AU - Gatch, Michael B.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Background: Substituted piperazines comprise a substantial proportion of the novel psychoactive substance market. Among the most widely abused piperazine compounds are meta-chlorophenylpiperazine (mCPP), tri-fluoromethylphenylpiperazine (TFMPP), and, especially, benzylpiperazine (BZP), which are commonly incorporated, either alone or in combination, in illicit “party pills” or “ecstasy” formulations. Illicit synthesis of BZP often results in production of an impure by-product dibenzylpiperazine (DBZP), which frequently appears alongside BZP in these formulations; however, despite its ubiquity, little information exists regarding the abuse liability of DBZP. Aims: The current study aimed to evaluate the abuse-related behavioral pharmacology of DBZP. Methods: DBZP, mCPP, and TFMPP were tested in parallel in mice in locomotor activity and conditioned place preference assays, and in a drug discrimination assay with rats trained to discriminate either methamphetamine, cocaine, (±)-3,4-methylenedioxymethamphetamine (MDMA), or -2,5-dimethoxy-4-methylamphetamine(DOM). Results: Each of the compounds tested produced dose-dependent decreases in locomotor activity. DBZP substituted fully for methamphetamine, produced subthreshold drug-appropriate responding for cocaine and MDMA, and failed to substitute for DOM. Conversely, TFMPP and mCPP only produced subthreshold drug-appropriate responding for methamphetamine and MDMA, respectively, and both compounds failed to substitute for cocaine or DOM. None of the compounds tested produced a place preference. DBZP produced convulsions in rats at the highest dose tested. Conclusions: These data indicate that DBZP is more similar to BZP, albeit with lower potency and efficacy, than its serotonergic piperazine counterparts, and is a behaviorally-active compound with some abuse liability and potential for adverse health effects.

AB - Background: Substituted piperazines comprise a substantial proportion of the novel psychoactive substance market. Among the most widely abused piperazine compounds are meta-chlorophenylpiperazine (mCPP), tri-fluoromethylphenylpiperazine (TFMPP), and, especially, benzylpiperazine (BZP), which are commonly incorporated, either alone or in combination, in illicit “party pills” or “ecstasy” formulations. Illicit synthesis of BZP often results in production of an impure by-product dibenzylpiperazine (DBZP), which frequently appears alongside BZP in these formulations; however, despite its ubiquity, little information exists regarding the abuse liability of DBZP. Aims: The current study aimed to evaluate the abuse-related behavioral pharmacology of DBZP. Methods: DBZP, mCPP, and TFMPP were tested in parallel in mice in locomotor activity and conditioned place preference assays, and in a drug discrimination assay with rats trained to discriminate either methamphetamine, cocaine, (±)-3,4-methylenedioxymethamphetamine (MDMA), or -2,5-dimethoxy-4-methylamphetamine(DOM). Results: Each of the compounds tested produced dose-dependent decreases in locomotor activity. DBZP substituted fully for methamphetamine, produced subthreshold drug-appropriate responding for cocaine and MDMA, and failed to substitute for DOM. Conversely, TFMPP and mCPP only produced subthreshold drug-appropriate responding for methamphetamine and MDMA, respectively, and both compounds failed to substitute for cocaine or DOM. None of the compounds tested produced a place preference. DBZP produced convulsions in rats at the highest dose tested. Conclusions: These data indicate that DBZP is more similar to BZP, albeit with lower potency and efficacy, than its serotonergic piperazine counterparts, and is a behaviorally-active compound with some abuse liability and potential for adverse health effects.

KW - Abuse liability

KW - DBZP

KW - conditioned place preference

KW - drug discrimination

UR - http://www.scopus.com/inward/record.url?scp=85048989869&partnerID=8YFLogxK

U2 - 10.1177/0269881118780613

DO - 10.1177/0269881118780613

M3 - Article

AN - SCOPUS:85048989869

VL - 32

SP - 802

EP - 810

JO - Journal of Psychopharmacology

JF - Journal of Psychopharmacology

SN - 0269-8811

IS - 7

ER -