The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain

Nagai, Fumiko; Nonaka, Ryouichi; Kamimura, Kanako Satoh Hisashi

doi:10.1016/j.ejphar.2006.11.075

Cited by 253 publications

(225 citation statements)

References 14 publications

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“…In particular, MDPV and cocaine exhibit lowefficacy 'partial'-releasing actions at DAT and NET (ie,o30% of maximal release), whereas amphetamine, mephedrone, and methylone are fully efficacious in their ability to evoke release of preloaded [ 3 H]MPP þ and [ 3 H]serotonin (ie, 100% of maximal release). The data with mephedrone and methylone agree with the published findings showing that these bath salts compounds are transporter substrates and not blockers (Baumann et al, 2012;Nagai et al, 2007;Sogawa et al, 2011). Based on previous observations, we surmised that the apparent releasing effects of MDPV and cocaine are secondary to uptake blockade, rather than substrate activity per se.…”

Section: Discussionsupporting

confidence: 81%

“…3,4-Methylenedioxypyrovalerone and monoamine transporters MH Baumann et al there are conflicting reports in the literature regarding the precise interactions of designer cathinones with monoamine transporters (Baumann et al, 2012;Cozzi et al, 1999;Hadlock et al, 2011;Martinez-Clemente et al, 2011;Nagai et al, 2007;Sogawa et al, 2011). Our results from in vitro experiments in synaptosomes confirm that uptake inhibition assays can identify drugs which interact with transporter proteins.…”

Section: Discussionsupporting

confidence: 78%

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Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products

Baumann

Partilla

Lehner

et al. 2012

Neuropsychopharmacol

371

453

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The abuse of psychoactive 'bath salts' containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods. In vitro transporter assays were performed in rat brain synaptosomes and in cells expressing human transporters, while clearance of endogenous dopamine was measured by fast-scan cyclic voltammetry in mouse striatal slices. Assessments of in vivo neurochemistry, locomotor activity, and cardiovascular parameters were carried out in rats. We found that MDPV blocks uptake of [ 3 H]dopamine (IC 50 ¼ 4.1 nM) and [ 3 H]norepinephrine (IC 50 ¼ 26 nM) with high potency but has weak effects on uptake of [ 3 H]serotonin (IC 50 ¼ 3349 nM). In contrast to other psychoactive cathinones (eg, mephedrone), MDPV is not a transporter substrate. The clearance of endogenous dopamine is inhibited by MDPV and cocaine in a similar manner, but MDPV displays greater potency and efficacy. Consistent with in vitro findings, MDPV (0.1-0.3 mg/kg, intravenous) increases extracellular concentrations of dopamine in the nucleus accumbens. Additionally, MDPV (0.1-3.0 mg/kg, subcutaneous) is at least 10 times more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. Our data show that MDPV is a monoamine transporter blocker with increased potency and selectivity for catecholamines when compared with cocaine. The robust stimulation of dopamine transmission by MDPV predicts serious potential for abuse and may provide a mechanism to explain the adverse effects observed in humans taking high doses of 'bath salts' preparations.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 78%

Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products

Baumann

Partilla

Lehner

et al. 2012

Neuropsychopharmacol

371

453

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“…During the preparation of this manuscript, Nagai et al (2007) published comparative data on the inhibition of monoamine transport in crude synaptosomes by a range of amphetamine derivatives, including BDB and MBDB. Direct comparison of their results and ours is difficult, since the experimental systems are not the same.…”

Section: Discussionmentioning

confidence: 99%

“…Direct comparison of their results and ours is difficult, since the experimental systems are not the same. The much lower IC 50 values quoted by Nagai et al (2007) 2,5-Dimethoxy-4-bromophenylethylamine (2CB) is similar to MBDB and BDB in that it too carries a modification of the a-methyl group on the amphetamine side chain. In this case, the a-methyl group has been removed resulting in a two-carbon, as opposed to a three-carbon, amphetamine side chain.…”

Section: Discussionmentioning

confidence: 99%

Comparative potencies of 3,4‐methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [³H]noradrenaline and [³H]5‐HT transport in mammalian cell lines

Montgomery

Buon

Eibauer

et al. 2007

British J Pharmacology

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Background and purpose: Illegal 'ecstasy' tablets frequently contain 3,4-methylenedioxymethamphetamine (MDMA)-like compounds of unknown pharmacological activity. Since monoamine transporters are one of the primary targets of MDMA action in the brain, a number of MDMA analogues have been tested for their ability to inhibit [ 3 H]noradrenaline uptake into rat PC12 cells expressing the noradrenaline transporter (NET) and [ 3 H]5-HT uptake into HEK293 cells stably transfected with the 5-HT transporter (SERT). Experimental approach: Concentration-response curves for the following compounds at both NET and SERT were determined under saturating substrate conditions: 4-hydroxy-3-methoxyamphetamine (HMA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxy-N-hydroxyamphetamine (MDOH), 2,5-dimethoxy-4-bromophenylethylamine (2CB), 3,4-dimethoxymethamphetamine (DMMA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), 3,4-methylenedioxyphenyl-N-methyl-2-butanamine (MBDB) and 2,3-methylenedioxymethamphetamine (2,3-MDMA). Key results: 2,3-MDMA was significantly less potent than MDMA at SERT, but equipotent with MDMA at NET. 2CB and BDB were both significantly less potent than MDMA at NET, but equipotent with MDMA at SERT. MBDB, DMMA, MDOH and the MDMA metabolites HMA and HMMA, were all significantly less potent than MDMA at both NET and SERT. Conclusions and implications:This study provides an important insight into the structural requirements of MDMA analogue affinity at both NET and SERT. It is anticipated that these results will facilitate understanding of the likely pharmacological actions of structural analogues of MDMA.

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“…While 2C-I does have some affinity at the 5HT 2A receptor, it binds more potently to the 5HT 2C receptor [5]. In addition, in vitro studies have demonstrated the ability of 2C-I to inhibit dopamine, serotonin, and norepinephrine re-uptake [6]. The 2C drugs are also agonists at the alpha-1 adrenergic receptor [1].…”

Section: Discussionmentioning

confidence: 99%

Recurrent Seizures and Serotonin Syndrome Following “2C-I” Ingestion

2013

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The phenethylamines, including 2, 5 dimethoxy-4-iodophenethylamine, commonly referred to as 2C-I, have recently emerged as a new class of designer drugs. Cases of toxicity from these drugs are not well described in the literature. This case report describes a 19 year-old male who insufflated 2C-I. Following the ingestion, the patient developed recurrent seizures, and was taken to the emergency department, where he was noted to be hyperadrenergic and had recurrent seizures. The patient was diagnosed with serotonin syndrome and experienced prolonged respiratory failure, although he ultimately made a full recovery. Comprehensive drug testing revealed the presence of 2C-I. The pharmacologic properties of 2C-I are also discussed.

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The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain

Cited by 253 publications

References 14 publications

Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products

Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products

Comparative potencies of 3,4‐methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [³H]noradrenaline and [³H]5‐HT transport in mammalian cell lines

Recurrent Seizures and Serotonin Syndrome Following “2C-I” Ingestion

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The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain

Cited by 253 publications

References 14 publications

Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products

Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products

Comparative potencies of 3,4‐methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [3H]noradrenaline and [3H]5‐HT transport in mammalian cell lines

Recurrent Seizures and Serotonin Syndrome Following “2C-I” Ingestion

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Comparative potencies of 3,4‐methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [³H]noradrenaline and [³H]5‐HT transport in mammalian cell lines